Updated on 2024/10/01

Information

 

写真a

 
MATSUSHIMA SHOJI
 
Organization
Kyushu University Hospital Angiocardiology Lecturer
School of Medicine Department of Medicine(Joint Appointment)
Title
Lecturer
Contact information
メールアドレス
Tel
0926425360
Profile
1.心不全・心筋症に関する基礎研究 2.心不全・心筋症の臨床研究 3.循環器疾患の診療 4.循環器領域の教育
External link

Degree

  • M.D., Ph.D.

Research Interests・Research Keywords

  • Research theme:1.Basic research of pathophysiology of heart failure 2.Clinical research of heart failure and cardiomyopathy 3. Omics analysis

    Keyword:heart failure, cardiomyophaty

    Research period: 2022.4 - 2025.3

  • Research theme:1. Organella regulation in cardiac remodeling 2. Post-translational modification of proteins in cardiac remodeling

    Keyword:mitochondria, heart failure

    Research period: 2021.4 - 2022.3

  • Research theme:1.Cardiac remodeling and organella regulation 2.Novel mechanism of protein post-translational modification in cardiac remodeling

    Keyword:Cardiac remodeling

    Research period: 2020.4 - 2020.3

  • Research theme:1.The regulatory mechanism of organella function 2.The role of post-translational modification and its regulatory mechanism

    Keyword:Cardiac remodeling

    Research period: 2019.4 - 2020.3

  • Research theme:1. ER stress in cardiac remodeling 2. MAM and heart failure 3. O'GacNacylation in cardiac remodeling

    Keyword:Cardiac remodeling

    Research period: 2018.4 - 2019.3

  • Research theme:1.A novel regulatory mechanism of ER stress in cardiac remodeling 2.The role of MAM in heart failure 3. The role of O'GlucNAcylation in cardiac remodeling

    Keyword:Heart failure

    Research period: 2017.4 - 2020.3

  • Research theme:1. The role of oxidative stress in cardiac remodelign and failure 2. Clinical feature of dilated phase of hypertrophic cardiomyopathy 3. Mechanism of mitochondrial quality control in heart failure 4. Eluciation of novel target and mechanism of cardiac remodeling

    Keyword:Heart failure, oxidative stress, mitochondria

    Research period: 2016.4 - 2017.3

Awards

  • 日本心臓財団拡張型心筋症研究奨励賞

    2019.3   日本心臓財団   日本心臓財団拡張型心筋症研究奨励賞

  • 第11回Vascular Biology Innovation Conference 最優秀賞

    2016.8   応用酵素協会   FynによるNox4の新たな制御機構の解明に関する研究に対して

Papers

  • Effectiveness of Vericiguat on right ventricle to pulmonary artery uncoupling associated with heart failure with reduced ejection fraction

    Hashimoto, T; Yoshitake, T; Suenaga, T; Yamamoto, S; Fujino, T; Shinohara, K; Matsushima, S; Ide, T; Kinugawa, S; Abe, K

    INTERNATIONAL JOURNAL OF CARDIOLOGY   415   132441   2024.11   ISSN:0167-5273 eISSN:1874-1754

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    Language:English   Publisher:International Journal of Cardiology  

    Backgrounds: A soluble guanylyl cyclase stimulator vericiguat has been shown to reduce cardiovascular mortality or hospitalization for heart failure in patients with worsening heart failure in the VICTORIA study. However, little is known about the effects of vericiguat on biventricular structure and function. Methods and results: A retrospective analysis of 63 consecutive patients with heart failure with reduced ejection fraction (HFrEF) who were treated with vericiguat was performed. Clinical data and echocardiographic parameters were compared between baseline and follow-up after the initiation of vericiguat. The median follow-up duration was 266 days. Treatment with vericiguat significantly reduced the plasma BNP levels (log-transformed) compared to baseline (2.46 ± 0.51 vs. 2.14 ± 0.58, p < 0.0001). Left ventricular end-diastolic volume index and left ventricular end-systolic volume index were significantly reduced (LVEDVI, 113.5 ± 46.3 vs. 103.6 ± 51.0, p = 0.0056; LVESVI, 82.0 ± 41.9 vs. 72.8 ± 44.7, p = 0.0077; respectively). The tricuspid annular plane systolic excursion to pulmonary artery systolic pressure (TAPSE/PASP) ratio, an indicator of right ventricle-pulmonary artery (RV-PA) coupling, increased significantly after the treatment (0.56 ± 0.29 vs. 0.92 ± 1.09, p < 0.0001). Univariate and multivariate analyses showed that the treatment effects of vericiguat on BNP levels, LV reverse remodeling, and RV-PA coupling were not correlated with the achievement of the quadruple therapy with beta-blockers, renin-angiotensin system inhibitors, mineralocorticoid inhibitors, and sodium-glucose cotransporter-2 inhibitors, nor with worsening heart failure (WHF). Conclusion: Treatment with vericiguat improved adverse LV remodeling and RV-PA uncoupling in HFrEF patients. These effects were independent of WHF and achieving the quadruple therapy. Patients with HFrEF may benefit from early initiation of vericiguat to prevent biventricular adverse remodeling.

    DOI: 10.1016/j.ijcard.2024.132441

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  • Different Impact of Immunosuppressive Therapy on Cardiac Outcomes in Systemic Versus Isolated Cardiac Sarcoidosis.

    Masunaga T, Hashimoto T, Fujino T, Ohtani K, Ishikawa Y, Yoshitake T, Shinohara K, Matsushima S, Ide T, Yamasaki Y, Isoda T, Baba S, Ishigami K, Tsutsui H, Kinugawa S

    International heart journal   65 ( 5 )   856 - 865   2024.9   ISSN:1349-2365

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    DOI: 10.1536/ihj.24-166

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  • Right Ventricular to Pulmonary Artery Uncoupling Is Associated With Impaired Exercise Capacity in Patients With Transthyretin Cardiac Amyloidosis.

    Hashimoto T, Ikuta K, Yamamoto S, Yoshitake T, Suenaga T, Nakashima S, Kai T, Misumi K, Fujino T, Shinohara K, Matsushima S, Atsumi R, Isoda T, Kinugawa S, Abe K

    Circulation journal : official journal of the Japanese Circulation Society   2024.9   ISSN:1346-9843

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    DOI: 10.1253/circj.CJ-24-0402

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  • Association of Multiple Nonhypertrophic Cardiomyopathy-Related Genetic Variants and Outcomes in Patients With Hypertrophic Cardiomyopathy.

    Hiruma T, Inoue S, Dai Z, Nomura S, Kubo T, Sugiura K, Suzuki A, Kashimura T, Matsushima S, Yamada T, Tobita T, Katoh M, Ko T, Ito M, Ishida J, Amiya E, Hatano M, Takeda N, Takimoto E, Akazawa H, Morita H, Yamaguchi J, Inomata T, Tsutsui H, Kitaoka H, Aburatani H, Takeda N, Komuro I

    JACC. Heart failure   2024.9   ISSN:2213-1779

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    DOI: 10.1016/j.jchf.2024.08.005

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  • Association Between Clonal Hematopoiesis and Left Ventricular Reverse Remodeling in Nonischemic Dilated Cardiomyopathy

    Inoue, S; Ko, T; Shindo, A; Nomura, S; Yamada, T; Jimba, T; Dai, ZH; Nakao, H; Suzuki, A; Kashimura, T; Iwahana, T; Goto, K; Matsushima, S; Ishida, J; Amiya, E; Zhang, B; Kubota, M; Sawami, K; Heryed, T; Yamada, S; Katoh, M; Katagiri, M; Ito, M; Nayakama, Y; Fujiu, K; Hatano, M; Takeda, N; Takimoto, E; Akazawa, H; Morita, H; Yamaguchi, J; Inomata, T; Kobayashi, Y; Minamino, T; Tsutsui, H; Kurokawa, M; Aiba, A; Aburatani, H; Komuro, I

    JACC-BASIC TO TRANSLATIONAL SCIENCE   9 ( 8 )   956 - 967   2024.8   ISSN:2452-302X

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    Language:English   Publisher:JACC: Basic to Translational Science  

    Although clonal hematopoiesis of indeterminate potential (CHIP) is an adverse prognostic factor for atherosclerotic disease, its impact on nonischemic dilated cardiomyopathy (DCM) is elusive. The authors performed whole-exome sequencing and deep target sequencing among 198 patients with DCM and detected germline mutations in cardiomyopathy-related genes and somatic mutations in CHIP driver genes. Twenty-five CHIP driver mutations were detected in 22 patients with DCM. Ninety-two patients had cardiomyopathy-related pathogenic mutations. Multivariable analysis revealed that CHIP was an independent risk factor of left ventricular reverse remodeling, irrespective of known prognostic factors. CHIP exacerbated cardiac systolic dysfunction and fibrosis in a DCM murine model. The identification of germline and somatic mutations in patients with DCM predicts clinical prognosis.

    DOI: 10.1016/j.jacbts.2024.04.010

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  • Esaxerenone: blood pressure reduction and cardiorenal protection without reflex sympathetic activation in salt-loaded stroke-prone spontaneously hypertensive rats

    Ikeda, S; Shinohara, K; Kashihara, S; Matsumoto, S; Yoshida, D; Nakashima, R; Ono, Y; Matsushima, S; Tsutsui, H; Kinugawa, S

    HYPERTENSION RESEARCH   47 ( 8 )   2133 - 2143   2024.8   ISSN:0916-9636 eISSN:1348-4214

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    Language:English   Publisher:Hypertension Research  

    Mineralocorticoid receptor (MR) is involved in the mechanisms of blood pressure elevation, organ fibrosis, and inflammation. MR antagonists have been used in patients with hypertension, heart failure, or chronic kidney disease. Esaxerenone, a recently approved MR blocker with a nonsteroidal structure, has demonstrated a strong blood pressure-lowering effect. However, blood pressure reduction may lead to sympathetic activation through the baroreflex. The effect of esaxerenone on the sympathetic nervous system remains unclear. We investigated the effect of esaxerenone on organ damage and the sympathetic nervous system in salt-loaded stroke-prone spontaneously hypertensive rats (SHRSP), a well-established model of essential hypertension with sympathoexcitation and organ damage. Three-week administration of esaxerenone or hydralazine successfully attenuated the blood pressure elevation. Both esaxerenone and hydralazine comparably suppressed left ventricular hypertrophy and urinary albumin excretion. However, renal fibrosis and glomerular sclerosis were suppressed by esaxerenone but not hydralazine. Furthermore, plasma norepinephrine level, a parameter of systemic sympathetic activity, was significantly increased by hydralazine but not by esaxerenone. Consistent with these findings, the activity of the control centers of sympathetic nervous system, the parvocellular region of the paraventricular nucleus in the hypothalamus and the rostral ventrolateral medulla, was enhanced by hydralazine but remained unaffected by esaxerenone. These results suggest that esaxerenone effectively lowers blood pressure without inducing reflex sympathetic nervous system activation. Moreover, the organ-protective effects of esaxerenone appear to be partially independent of its blood pressure-lowering effect. In conclusion, esaxerenone demonstrates a blood pressure-lowering effect without concurrent sympathetic activation and exerts organ-protective effects in salt-loaded SHRSP. (Figure presented.)

    DOI: 10.1038/s41440-024-01733-4

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  • Management and outcomes of heart failure hospitalization among older adults in the United States and Japan

    Bates, BA; Enzan, N; Tohyama, T; Gandhi, P; Matsushima, S; Tsutsui, H; Setoguchi, S; Ide, T

    ESC HEART FAILURE   11 ( 5 )   3395 - 3405   2024.7   ISSN:2055-5822

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    Aims: Despite advances in therapies, the disease burden of heart failure (HF) has been rising globally. International comparisons of HF management and outcomes may reveal care patterns that improve outcomes. Accordingly, we examined clinical management and patient outcomes in older adults hospitalized for acute HF in the United States (US) and Japan. Methods: We identified patients aged >65 who were hospitalized for HF in 2013 using US Medicare data and the Japanese Registry of Acute Decompensated Heart Failure (JROADHF). We described patient characteristics, management, and healthcare utilization and compared outcomes using multivariable Cox regression during and after HF hospitalization. Results: Among 11 193 Japanese and 120 289 US patients, age and sex distributions were similar, but US patients had higher comorbidity rates. The length of stay was longer in Japan (median 18 vs. 5 days). While Medicare patients had higher use of implantable cardioverter defibrillator or cardiac resynchronization therapy during hospitalization (1.32% vs. 0.6%), Japanese patients were more likely to receive cardiovascular medications at discharge and to undergo cardiac rehabilitation within 3 months of HF admission (31% vs. 1.6%). Physician follow-up within 30 days was higher in Japan (77% vs. 57%). Cardiovascular readmission, cardiovascular mortality and all-cause mortality were 2.1–3.7 times higher in the US patients. The per-day cost of hospitalization was lower in Japan ($516 vs. $1323). Conclusions: We observed notable differences in the management, outcomes and costs of HF hospitalization between the US and Japan. Large differences in length of hospitalization, cardiac rehabilitation rate and outcomes warrant further research to determine the optimal length of stay and assess the benefits of inpatient cardiac rehabilitation to reduce rehospitalization and mortality.

    DOI: 10.1002/ehf2.14873

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  • Hemoglobin Level Can Predict Heart Failure Hospitalization in Patients with Advanced Heart Failure Awaiting Heart Transplantation without Inotropes or Mechanical Circulatory Support

    Suenaga, T; Fujino, T; Hashimoto, T; Ishikawa, Y; Shinohara, K; Matsushima, S; Komman, H; Toyosawa, M; Ide, T; Tsutsui, H; Shiose, A; Kinugawa, S

    INTERNATIONAL HEART JOURNAL   65 ( 4 )   667 - 675   2024.7   ISSN:1349-2365 eISSN:1349-3299

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    Although anemia is a common comorbidity that often coexists with heart failure (HF), its clinical impact in patients with advanced HF remains unclear. We investigated the impact of hemoglobin levels on clinical outcomes in patients with advanced HF listed for heart transplantation without intravenous inotropes or mechanical circulatory support. We retrospectively reviewed the clinical data of patients listed for heart transplantation at our institute who did not receive intravenous inotropes or mechanical circulatory support between 2011 and 2022. We divided the patients into those with hemoglobin levels lower or higher than the median value and compared the composite of all-cause death and HF hospitalization within 1 year from the listing date. We enrolled consecutive 38 HF patients (27 males, 49.1 ± 10.8 years old). The median hemoglobin value at the time of listing for heart transplantation was 12.9 g/dL, and 66.7% of the patients had iron deficiency. None of the patients in either group died within 1 year. The HF hospitalization-free survival rate was significantly lower in the lower hemoglobin group (40.9% versus 81.9% at 1 year, P = 0.020). Multivariate Cox proportional hazards model analysis showed that hemoglobin as a continuous variable was an independent predictor for HF hospitalization (odds ratio 0.70, 95% confidence interval 0.49-0.97, P = 0.030). Hemoglobin level at the time of listing for heart transplantation was a predictor of hospitalization in heart-transplant candidates without intravenous inotropes or mechanical circulatory support.

    DOI: 10.1536/ihj.24-067

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  • Atrial fibrillation type and long-term clinical outcomes in hospitalized patients with heart failure: insight from JROADHF

    Hamatani, Y; Enzan, N; Iguchi, M; Yoshizawa, T; Kawaji, T; Ide, T; Tohyama, T; Matsushima, S; Abe, M; Tsutsui, H; Akao, M

    EUROPEAN HEART JOURNAL-QUALITY OF CARE AND CLINICAL OUTCOMES   10 ( 3 )   193 - 202   2024.5   ISSN:2058-5225 eISSN:2058-1742

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    Language:English   Publisher:European Heart Journal - Quality of Care and Clinical Outcomes  

    Aims: Atrial fibrillation (AF) type (paroxysmal, persistent, or permanent) is important in determining therapeutic management; however, clinical outcomes by AF type are largely unknown for hospitalized patients with heart failure (HF). Methods and results: The Japanese Registry Of Acute Decompensated Heart Failure is a retrospective, multicenter, and nationwide registry of patients hospitalized for acute HF in Japan. Follow-up data were collected up to 5 years after hospitalization. Patients were divided based on diagnosis and AF type into 3 groups [without AF, paroxysmal AF, and sustained AF (defined as a composite of persistent and permanent AF)], and compared the backgrounds and outcomes between the groups. Of 12 895 hospitalized HF patients [mean age: 78 ± 13 years, female: 6077 (47%), and mean left ventricular ejection fraction: 47 ± 17%], 1725 had paroxysmal AF, and 3672 had sustained AF. Compared with patients without AF, sustained AF had a higher risk of the primary composite endpoint of cardiovascular (CV) death or HF hospitalization [hazard ratio (HR): 1.09, 95% confidence interval (CI): 1.01-1.17; P = 0.03], mainly driven by HF hospitalization [HR: 1.16, 95% CI: 1.06-1.26; P < 0.001], whereas the corresponding risk for the primary endpoint in patients with paroxysmal AF was not elevated (HR: 1.03, 95% CI: 0.94-1.13; P = 0.53) after adjustment by multivariable Cox regression analysis. These results were consistent among the subgroups of patients with reduced or preserved ejection fraction (interaction P = 0.74). Conclusion: Among hospitalized patients with HF, sustained AF, but not paroxysmal AF, was significantly associated with a higher risk for CV death or HF hospitalization, indicating the importance of accounting for AF type in HF patients.

    DOI: 10.1093/ehjqcco/qcae005

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  • <SUP>18</SUP>F-Fluorodeoxyglucose Positron Emission Tomography Can be a Novel Diagnostic Tool for Detecting Acute Cellular Rejection Following Heart Transplantation

    Yoshitake, T; Fujino, T; Yamamoto, S; Hashimoto, T; Suenaga, T; Shinohara, K; Matsushima, S; Kitamura, Y; Komman, H; Toyosawa, M; Ide, T; Shiose, A; Kinugawa, S

    JOURNAL OF HEART AND LUNG TRANSPLANTATION   43 ( 4 )   S206 - S206   2024.4   ISSN:1053-2498 eISSN:1557-3117

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  • Overview of the 87th Annual Scientific Meeting of the Japanese Circulation Society (JCS2023) ― New Challenge With Next Generation ―

    Matoba, T; Nakano, Y; Katsuki, S; Ide, T; Matsushima, S; Fujino, T; Hashimoto, T; Shinohara, K; Abe, K; Hosokawa, K; Sakamoto, T; Sakamoto, I; Kakino, T; Ishikita, A; Nishizaki, A; Sakamoto, K; Takase, S; Nagayama, T; Tohyama, T; Nagata, T; Kinugawa, S; Tsutsui, H

    CIRCULATION JOURNAL   88 ( 4 )   615 - 619   2024.4   ISSN:1346-9843 eISSN:1347-4820

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    Language:English   Publisher:Circulation Journal  

    The 87th Annual Meeting of the Japanese Circulation Society (JCS2023) was held in March 2023 in Fukuoka, Japan, marking the first in-person gathering after the COVID-19 pandemic. With the theme of “New Challenge With Next Generation” the conference emphasized the development of future cardiovascular leaders and technologies such as artificial intelligence (AI). Notable sessions included the Mikamo Lecture on heart failure and the Mashimo Lecture on AI in medicine. Various hands-on sessions and participatory events were well received, promoting learning and networking. Post-event surveys showed high satisfaction among participants, with positive feedback on face-to-face interactions and the overall experience. JCS2023, attended by 17,852 participants, concluded successfully, marking a significant milestone in post-pandemic meetings, and advancing cardiovascular medicine.

    DOI: 10.1253/circj.CJ-24-0127

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  • Development of deep-learning models for real-time anaerobic threshold and peak VO<sub>2</sub> prediction during cardiopulmonary exercise testing

    Watanabe, T; Tohyama, T; Ikeda, M; Fujino, T; Hashimoto, T; Matsushima, S; Kishimoto, J; Todaka, K; Kinugawa, S; Tsutsui, H; Ide, T

    EUROPEAN JOURNAL OF PREVENTIVE CARDIOLOGY   31 ( 4 )   448 - 457   2024.3   ISSN:2047-4873 eISSN:2047-4881

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    Language:English   Publisher:European Journal of Preventive Cardiology  

    Aims Exercise intolerance is a clinical feature of patients with heart failure (HF). Cardiopulmonary exercise testing (CPET) is the first-line examination for assessing exercise capacity in patients with HF. However, the need for extensive experience in assessing anaerobic threshold (AT) and the potential risk associated with the excessive exercise load when measuring peak oxygen uptake (peak VO2) limit the utility of CPET. This study aimed to use deep-learning approaches to identify AT in real time during testing (defined as real-time AT) and to predict peak VO2 at real-time AT. Methods and results This study included the time-series data of CPET recorded at the Department of Cardiovascular Medicine, Kyushu University Hospital. Two deep neural network models were developed to: (i) estimate the AT probability using breath-by-breath data and (ii) predict peak VO2 using the data at the real-time AT. The eligible CPET contained 1472 records of 1053 participants aged 18–90 years and 20% were used for model evaluation. The developed model identified real-time AT with 0.82 for correlation coefficient (Corr) and 1.20 mL/kg/min for mean absolute error (MAE), and the corresponding AT time with 0.86 for Corr and 0.66 min for MAE. The peak VO2 prediction model achieved 0.87 for Corr and 2.25 mL/kg/min for MAE. Conclusion Deep-learning models for real-time CPET analysis can accurately identify AT and predict peak VO2. The developed models can be a competent assistant system to assess a patient’s condition in real time, expanding CPET utility.

    DOI: 10.1093/eurjpc/zwad375

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  • Evaluation of the A<sub>2</sub>B Score for Prediction of Survival in Patients With Heart Failure in a Nationwide Cohort in Japan

    Kyodo, A; Nakada, Y; Nogi, M; Nogi, K; Ishihara, S; Ueda, T; Tohyama, T; Enzan, N; Ide, T; Matsushima, S; Tsutsui, H; Saito, Y

    JOURNAL OF THE AMERICAN HEART ASSOCIATION   13 ( 4 )   e031104   2024.2   eISSN:2047-9980

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    BACKGROUND: Although a tool for sharing patient prognosis among all medical staff is desirable in heart failure (HF) cases, only a few simple HF prognostic scores are available. We previously presented the A2 B score, a simple user-friendly HF risk score, and validated it in a small single-center cohort. In the present study, we validated it in a larger nationwide cohort. METHODS AND RESULTS: We examined the 2-year mortality in relation to the A2 B scores in 3483 patients from a Japanese nationwide cohort and attempted to stratify their prognoses according to the scores. The A2 B score was determined by assign-ing points for age, anemia, and brain natriuretic peptide (BNP) level at discharge: age (<65 years, 0; 65–74 years, 1; ≥75 years, 2), anemia (hemoglobin ≥12 g/dL, 0; 10–11.9 g/dL, 1; <10 g/dL, 2), and BNP (<200 pg/mL, 0; 200–499 pg/mL, 1; ≥500 pg/mL, 2). Hemoglobin and BNP levels were applied to the data at discharge. The 2-year survival rates for A2 B scores 1, 2, 3, 4, 5, and 6 were 94.1%, 83.2%, 74.1%, 63.5%, 51.6%, and 41.5%, respectively; the mortality rate increased by ≈10% for each point increase (c-index, 0.702). The A2 B score was applicable in HF cases with reduced or preserved ejection fraction and remained useful when BNP was substituted with N-terminal proBNP (c-index, 0.749, 0.676, and 0.682, respectively). CONCLUSIONS: The A2 B score showed a good prognostic value for HF in a large population even when BNP was replaced with N-terminal proBNP.

    DOI: 10.1161/JAHA.123.031104

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  • Association of baseline electrocardiographic left ventricular hypertrophy with future renal function decline in the general population

    Ikeda, S; Shinohara, K; Tagawa, K; Tohyama, T; Kishimoto, J; Kazurayama, M; Tanaka, S; Yamaizumi, M; Nagayoshi, H; Toyama, K; Matsushima, S; Tsutsui, H; Kinugawa, S

    SCIENTIFIC REPORTS   14 ( 1 )   301   2024.1   ISSN:2045-2322

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    Electrocardiographic left ventricular hypertrophy (LVH) could predict adverse renal outcomes in patients with hypertension. This study aimed to investigate the association between electrocardiographic LVH and future decline in renal function in the general population using a dataset of population-based health checkups from 2010 to 2019 including 19,825 participants. Electrocardiographic LVH was defined according to the Minnesota code. Renal function decline was defined as a decrease of ≥ 25% in the estimated glomerular filtration rate from baseline to < 60 mL/min/1.73 m2. Electrocardiographic LVH was found in 1263 participants at the baseline visit. The mean follow-up period was 3.4 ± 1.9 years. The incidence rates of renal function decline were 0.30 and 0.78 per 100 person-years in the non-LVH group and LVH groups, respectively. Electrocardiographic LVH was associated with the risk for renal function decline in the adjusted analysis (hazard ratio 1.69, 95% confidence interval 1.14–2.50, P = 0.009). This association was comparable across subgroups stratified by age, sex, body mass index, diagnosed hypertension, systolic blood pressure, hemoglobin A1c, and urinary protein. This study underscores the usefulness of electrocardiographic LVH to detect high-risk individuals for renal function decline in the setting of health checkups in the general population.

    DOI: 10.1038/s41598-023-51085-1

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  • Deferasirox Targeting Ferroptosis Synergistically Ameliorates Myocardial Ischemia Reperfusion Injury in Conjunction With Cyclosporine A

    Ishimaru, K; Ikeda, M; Miyamoto, HD; Furusawa, S; Abe, K; Watanabe, M; Kanamura, T; Fujita, S; Nishimura, R; Toyohara, T; Matsushima, S; Koumura, T; Yamada, K; Imai, H; Tsutsui, H; Ide, T

    JOURNAL OF THE AMERICAN HEART ASSOCIATION   13 ( 1 )   e031219   2024.1   eISSN:2047-9980

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    BACKGROUND: Ferroptosis, an iron-dependent form of regulated cell death, is a major cell death mode in myocardial ischemia reperfusion (I/R) injury, along with mitochondrial permeability transition-driven necrosis, which is inhibited by cyclosporine A (CsA). However, therapeutics targeting ferroptosis during myocardial I/R injury have not yet been developed. Hence, we aimed to investigate the therapeutic efficacy of deferasirox, an iron chelator, against hypoxia/reoxygenation-induced ferroptosis in cultured cardiomyocytes and myocardial I/R injury. METHODS AND RESULTS: The effects of deferasirox on hypoxia/reoxygenation-induced iron overload in the endoplasmic reticulum, lipid peroxidation, and ferroptosis were examined in cultured cardiomyocytes. In a mouse model of I/R injury, the infarct size and adverse cardiac remodeling were examined after treatment with deferasirox, CsA, or both in combination. Deferasirox suppressed hypoxia-or hypoxia/reoxygenation-induced iron overload in the endoplasmic reticulum, lipid peroxidation, and ferroptosis in cultured cardiomyocytes. Deferasirox treatment reduced iron levels in the endoplasmic reticulum and prevented increases in lipid peroxidation and ferroptosis in the I/R-injured myocardium 24 hours after I/R. Deferasirox and CsA independently reduced the infarct size after I/R injury to a similar degree, and combination therapy with deferasirox and CsA synergistically reduced the infarct size (infarct area/area at risk; control treatment: 64±2%; deferasirox treatment: 48±3%; CsA treatment: 48±4%; deferasirox+CsA treatment: 37±3%), thereby ameliorating adverse cardiac remodeling on day 14 after I/R. CONCLUSIONS: Combination therapy with deferasirox and CsA may be a clinically feasible and effective therapeutic approach for limiting I/R injury and ameliorating adverse cardiac remodeling after myocardial infarction.

    DOI: 10.1161/JAHA.123.031219

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  • Cardiac Autoantibodies Against Cardiac Troponin I in Post-Myocardial Infarction Heart Failure: Evaluation in a Novel Murine Model and Applications in Therapeutics

    Furusawa, S; Ikeda, M; Ide, T; Kanamura, T; Miyamoto, HD; Abe, K; Ishimaru, K; Watanabe, M; Tsutsui, Y; Miyake, R; Fujita, S; Tohyama, T; Matsushima, S; Baba, Y; Tsutsui, H

    CIRCULATION-HEART FAILURE   16 ( 10 )   895 - 908   2023.10   ISSN:1941-3289 eISSN:1941-3297

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    BACKGROUND: Cardiac autoantibodies (cAAbs) are involved in the progression of adverse cardiac remodeling in heart failure (HF). However, our understanding of cAAbs in HF is limited owing to the absence of relevant animal models. Herein, we aimed to establish and characterize a murine model of cAAb-positive HF after myocardial infarction (MI), thereby facilitating the development of therapeutics targeting cAAbs in post-MI HF. METHODS: MI was induced in BALB/c mice. Plasma cAAbs were evaluated using modified Western blot-based methods. Prognosis, cardiac function, inflammation, and fibrosis were compared between cAAb-positive and cAAb-negative MI mice. Rapamycin was used to inhibit cAAb production. RESULTS: Common cAAbs in BALB/c MI mice targeted cTnI (cardiac troponin I). Herein, 71% (24/34) and 44% (12/27) of the male and female MI mice, respectively, were positive for cAAbs against cTnI (cTnIAAb). Germinal centers were formed in the spleens and mediastinal lymph nodes of cTnIAAb-positive MI mice. cTnIAAb-positive MI mice showed progressive cardiac remodeling with a worse prognosis (P=0.014, by log-rank test), which was accompanied by cardiac inflammation, compared with that in cTnIAAb-negative MI mice. Rapamycin treatment during the first 7 days after MI suppressed cTnIAAb production (cTnIAAb positivity, 59% [29/49] and 7% [2/28] in MI mice treated with vehicle and rapamycin, respectively; P<0.001, by Pearson χ2 test), consequently improving the survival and ameliorating cardiac inflammation, cardiac remodeling, and HF in MI mice. CONCLUSIONS: The present post-MI HF model may accelerate our understanding of cTnIAAb and support the development of therapeutics against cTnIAAbs in post-MI HF.

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  • Regional Variation in the Clinical Practice and Prognosis in Patients With Heart Failure With Reduced Ejection Fraction in Japan ― A Report From the Japanese Registry of Acute Decompensated Heart Failure (JROADHF)

    Sato, Y; Yoshihisa, A; Ide, T; Tohyama, T; Enzan, N; Matsushima, S; Tsutsui, H; Takeishi, Y

    CIRCULATION JOURNAL   87 ( 10 )   1380 - +   2023.10   ISSN:1346-9843 eISSN:1347-4820

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    Background: The present study aimed to clarify the regional variations in clinical practice and the prognosis of patients with heart failure with reduced ejection fraction (HFrEF) in Japan using the Japanese Registry of Acute Decompensated Heart Failure (JROADHF). Methods and Results: We recruited data of hospitalized patients with HFrEF (n=4, 329) from the JROADHF. The patients were divided into 6 groups based on the region of Japan where they were hospitalized: Hokkaido-Tohoku (n=504), Kanto (n=958), Chubu (n=779), Kinki (n=902), Chugoku-Shikoku (n=446), and Kyushu (n=740). We compared the patients' characteristics, including etiology of HF and prognosis after discharge. The age of the patients was lowest in the Kanto and Kinki regions. In contrast, there were no differences in the prevalence of comorbidities, levels of B-type natriuretic peptide, or left ventricular EF among the 6 groups. Post-discharge cardiospecific prognosis, specifically, the composite of cardiac death or HF hospitalization, cardiac death, and HF hospitalization, was comparable among the 6 regions. Conclusions: There were no differences in cardiospecific prognosis in patients with HFrEF among the 6 regions in Japan.

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  • Efficacy of Early Catheter Ablation for Atrial Fibrillation After Admission for Heart Failure

    Sakamoto, K; Tohyama, T; Ide, T; Mukai, Y; Enzan, N; Nagata, T; Ikeda, M; Takase, S; Nagayama, T; Fujino, T; Matsushima, S; Tsutsui, H

    JACC-CLINICAL ELECTROPHYSIOLOGY   9 ( 9 )   1948 - 1959   2023.9   ISSN:2405-500X eISSN:2405-5018

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    Background: Advances in catheter ablation (CA) for atrial fibrillation (AF) have improved the prognosis of patients with heart failure (HF) and AF. However, its optimal timing remains to be fully elucidated. Objectives: The aim of this study was to investigate the prognostic impact of early CA in patients with HF and AF hospitalized for worsening HF. Methods: From JROADHF (Japanese Registry of Acute Decompensated Heart Failure) (n = 13,238), patients with HF and AF who underwent CA within 90 days after admission for HF (early CA; n = 103) and those who did not (control; n = 2,683) were identified. Mortality was compared between these groups in the crude cohort, as well as in the propensity-matched cohort (n = 83 in each group). Results: In the crude cohort, all-cause mortality was significantly lower in the early CA group than in the control group (log-rank P < 0.001; HR: 0.38; 95% CI: 0.24-0.60). In the matched cohort, all-cause mortality was likewise significantly lower in the early CA group (log-rank P = 0.014; HR: 0.47; 95% CI: 0.25-0.88). Cardiovascular death and HF mortality were significantly lower in both cohorts (crude: Gray’ test: P < 0.001 and P = 0.005; subdistribution HR: 0.28 [95% CI: 0.13-0.63] and HR: 0.31 [95% CI: 0.13-0.75]; matched: Gray's test: P = 0.006 and P = 0.017; subdistribution HR: 0.24 [95% CI: 0.08-0.70] and HR: 0.28 [95% CI: 0.09-0.84], respectively). Conclusions: In a nationwide representative real-world cohort, CA for AF within 90 days after admission for HF was associated with improved long-term outcomes, including cardiovascular and HF death in patients with HF and AF.

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  • IFN-g-STAT1-ERK Pathway Mediates Protective Effects of Invariant Natural Killer T Cells Against Doxorubicin-Induced Cardiomyocyte Death

    Sada, M; Matsushima, S; Ikeda, M; Ikeda, S; Okabe, K; Ishikita, A; Tadokoro, T; Enzan, N; Yamamoto, T; Miyamoto, HD; Tsutsui, Y; Miyake, R; Setoyama, D; Kang, D; Ide, T; Tsutsui, H

    JACC-BASIC TO TRANSLATIONAL SCIENCE   8 ( 8 )   992 - 1007   2023.8   ISSN:2452-302X

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    Doxorubicin (DOX)-induced cardiomyopathy has poor prognosis, and myocardial inflammation is intimately involved in its pathophysiology. The role of invariant natural killer T (iNKT) cells has not been fully determined in this disease. We here demonstrated that activation of iNKT cells by α-galactosylceramide (GC) attenuated DOX-induced cardiomyocyte death and cardiac dysfunction. αGC increased interferon (IFN)-γ and phosphorylation of signal transducers and activators of transcription 1 (STAT1) and extracellular signal-regulated kinase (ERK). Administration of anti-IFN-γ neutralizing antibody abrogated the beneficial effects of αGC on DOX-induced cardiac dysfunction. These findings emphasize the protective role of iNKT cells in DOX-induced cardiomyopathy via the IFN-γ-STAT1-ERK pathway.

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  • An increasing trend of gastric cancer deaths and inadequate preventive measures in elderly adults

    Matsushima, R; Matsushima, S; Kobayashi, M; Fujimori, K; Sakamoto, N; Asaka, M

    HELICOBACTER   28 ( 4 )   e12988   2023.8   ISSN:1083-4389 eISSN:1523-5378

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    Background: Japan became the world's first country to cover Helicobacter pylori eradication for chronic gastritis under its National Health Insurance (NHI) system in February 2013. Thereafter, H. pylori eradication dramatically increased and gastric cancer deaths began to decrease in Japan. However, the details of gastric cancer deaths and its prevention in the very elderly have not been fully elucidated. Methods: We analyzed the temporal trend of gastric cancer deaths referencing data from Ministry of Health, Labour and Welfare reports and “Cancer Statistics in Japan–2021” and assessed the numbers of H. pylori test and gastric cancer screening using a national database and a report of cancer screening in Shimane Prefecture, respectively. Results: Although gastric cancer deaths in total population have clearly decreased since 2013, those in people aged 80 years and older are still increasing. People aged 80 years and older represent 9% of the total population and accounted for half of all gastric cancer deaths in 2020. The numbers of H. pylori eradication and gastric cancer screening in people aged 80 years and older were 25% and 25% of those in other generations, respectively. Conclusion: In spite of a dramatic increase in H. pylori eradication and a clear decrease in gastric cancer deaths in Japan, gastric cancer deaths in people aged 80 years and older are increasing. This might be due to fewer H. pylori eradication in the elderly than in other generations, indicating the difficulty of gastric cancer prevention in the very elderly.

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  • Prevalence, characteristics and cardiovascular and non-cardiovascular outcomes in patients with heart failure with supra-normal ejection fraction: Insight from the JROADHF study

    Horiuchi, Y; Asami, M; Ide, T; Yahagi, K; Komiyama, K; Yuzawa, H; Tanaka, J; Aoki, J; Matsushima, S; Tohyama, T; Enzan, N; Tsutsui, H; Tanabe, K

    EUROPEAN JOURNAL OF HEART FAILURE   25 ( 7 )   989 - 998   2023.7   ISSN:1388-9842 eISSN:1879-0844

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    Aims: We aimed to investigate the characteristics and prognosis of patients with heart failure (HF) with supra-normal ejection fraction (HFsnEF) compared to HF with normal ejection fraction (HFnEF). Methods and results: Among 11 573 patients enrolled in the nationwide registry of hospitalized patients with HF in Japan, 1943 patients (16.8%) were classified as HFsnEF (left ventricular ejection fraction [LVEF] >65%), 3277 (28.3%) as HFnEF (50% ≤ LVEF ≤65%), 2024 (17.5%) as HF with mildly reduced ejection fraction (40% ≤ LVEF <50%) and 4329 (37.4%) as HF with reduced ejection fraction (LVEF <40%). Patients with HFsnEF were older, more likely to be women, had lower natriuretic peptide values, and had smaller left ventricles than those with HFnEF. The primary endpoint, the composite of cardiovascular death or HF readmission, did not differ between HFsnEF (802/1943, 41.3%) and HFnEF (1413/3277, 43.1%) during a median follow-up period of 870 days (hazard ratio [HR] 0.96, 95% confidence interval 0.88–1.05, p = 0.346). The incidence of secondary outcomes, including all-cause, cardiovascular, and non-cardiovascular deaths and HF readmission, did not differ between HFsnEF and HFnEF. In the multivariable Cox regression analysis, HFsnEF compared to HFnEF was associated with a lower adjusted HR for HF readmission but not with the primary and other secondary endpoints. HFsnEF was associated with a higher HR for the composite endpoint and all-cause death in women, and a higher HR for all-cause death in patients with renal dysfunction. Conclusions: Heart failure with supra-normal ejection fraction is a common and distinctive phenotype, and has different characteristics and prognoses from HFnEF.

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  • IFN-γ-STAT1-ERK Pathway Mediates Protective Effects of Invariant Natural Killer T Cells Against Doxorubicin-Induced Cardiomyocyte Death Reviewed International journal

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  • Doxorubicin causes ferroptosis and cardiotoxicity by intercalating into mitochondrial DNA and disrupting Alas1-dependent heme synthesis. Invited Reviewed International journal

    Abe K, Ikeda M, Ide T, Tadokoro T, Miyamoto HD, Furusawa S, Tsutsui Y, Miyake R, Ishimaru K, Watanabe M, Matsushima S, Koumura T, Yamada KI, Imai H, Tsutsui H

    Sci Signal   2023.6

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  • A higher resting heart rate is associated with cardiovascular event risk in patients with type 2 diabetes mellitus without known cardiovascular disease

    Ikeda, S; Shinohara, K; Enzan, N; Matsushima, S; Tohyama, T; Funakoshi, K; Kishimoto, J; Itoh, H; Komuro, I; Tsutsui, H

    HYPERTENSION RESEARCH   46 ( 5 )   1090 - 1099   2023.5   ISSN:0916-9636 eISSN:1348-4214

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    A higher resting heart rate (RHR) is associated with an increased risk of cardiovascular events in patients with type 2 diabetes mellitus (T2DM) and cardiovascular diseases. The aim of this study was to investigate the association between RHR and cardiovascular events in T2DM patients with diabetic retinopathy and without known cardiovascular disease. We analyzed the association between RHR and cardiovascular events, including coronary, cerebral, renal and vascular events or cardiovascular death in T2DM patients with retinopathy and hyperlipidemia without prior cardiovascular events who were enrolled in the EMPATHY study. Data from 4746 patients were analyzed. The median RHR was 76 bpm. Patients were divided into four groups based on their baseline RHR (< 60, 60–69, 70–79, and ≥80 bpm). Patients with a higher RHR were more likely to be younger and had a higher body mass index, blood pressure value, HbA1c value, and estimated glomerular filtration rate and a lower B-type natriuretic peptide value; they also had a higher proportion of current smoking status, neuropathy, and nephropathy. After adjusting for confounders, including the aforementioned risk factors, a RHR of 70–79 bpm and a RHR ≥ 80 bpm were significantly associated with cardiovascular events (hazard ratio 1.50, 95% CI 1.03–2.20; and hazard ratio 1.62, 95% CI 1.11–2.36; respectively) compared to a RHR of 60–69 bpm. The analysis using restricted cubic splines indicated that the cardiovascular risk seemed to be similarly high when the RHR range was ≥70 bpm. In conclusion, in T2DM patients with diabetic retinopathy and without known cardiovascular disease, a high RHR, particularly ≥70 bpm, was associated with the risk of cardiovascular events compared to a RHR of 60–69 bpm. [Figure not available: see fulltext.].

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  • ZBP1 Protects Against mtDNA-Induced Myocardial Inflammation in Failing Hearts

    Enzan, N; Matsushima, S; Ikeda, S; Okabe, K; Ishikita, A; Yamamoto, T; Sada, M; Miyake, R; Tsutsui, Y; Nishimura, R; Toyohara, T; Ikeda, Y; Shojima, Y; Miyamoto, HD; Tadokoro, T; Ikeda, M; Abe, K; Ide, T; Kinugawa, S; Tsutsui, H

    CIRCULATION RESEARCH   132 ( 9 )   1110 - 1126   2023.4   ISSN:0009-7330 eISSN:1524-4571

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    Background: Mitochondrial DNA (mtDNA)-induced myocardial inflammation is intimately involved in cardiac remodeling. ZBP1 (Z-DNA binding protein 1) is a pattern recognition receptor positively regulating inflammation in response to mtDNA in inflammatory cells, fibroblasts, and endothelial cells. However, the role of ZBP1 in myocardial inflammation and cardiac remodeling remains unclear. The aim of this study was to elucidate the role of ZBP1 in mtDNA-induced inflammation in cardiomyocytes and failing hearts. Methods: mtDNA was administrated into isolated cardiomyocytes. Myocardial infarctionwas conducted in wild type and ZBP1 knockout mice. Results: We here found that, unlike in macrophages, ZBP1 knockdown unexpectedly exacerbated mtDNA-induced inflammation such as increases in IL (interleukin)-1β and IL-6, accompanied by increases in RIPK3 (receptor interacting protein kinase 3), phosphorylated NF-κB (nuclear factor-κB), and NLRP3 (nucleotide-binding domain and leucine-rich-repeat family pyrin domain containing 3) in cardiomyocytes. RIPK3 knockdown canceled further increases in phosphorylated NF-κB, NLRP3, IL-1β, and IL-6 by ZBP1 knockdown in cardiomyocytes in response to mtDNA. Furthermore, NF-κB knockdown suppressed such increases in NLRP3, IL-1β, and IL-6 by ZBP1 knockdown in response to mtDNA. CpG-oligodeoxynucleotide, a Toll-like receptor 9 stimulator, increased RIPK3, IL-1β, and IL-6 and ZBP1 knockdown exacerbated them. Dloop, a component of mtDNA, but not Tert and B2m, components of nuclear DNA, was increased in cytosolic fraction from noninfarcted region of mouse hearts after myocardial infarction compared with control hearts. Consistent with this change, ZBP1, RIPK3, phosphorylated NF-κB, NLRP3, IL-1β, and IL-6 were increased in failing hearts. ZBP1 knockout mice exacerbated left ventricular dilatation and dysfunction after myocardial infarction, accompanied by further increases in RIPK3, phosphorylated NF-κB, NLRP3, IL-1β, and IL-6. In histological analysis, ZBP1 knockout increased interstitial fibrosis and myocardial apoptosis in failing hearts. Conclusions: Our study reveals unexpected protective roles of ZBP1 against cardiac remodeling as an endogenous suppressor of mtDNA-induced myocardial inflammation.

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  • RPL3L-containing ribosomes determine translation elongation dynamics required for cardiac function

    Shiraishi, C; Matsumoto, A; Ichihara, K; Yamamoto, T; Yokoyama, T; Mizoo, T; Hatano, A; Matsumoto, M; Tanaka, Y; Matsuura-Suzuki, E; Iwasaki, S; Matsushima, S; Tsutsui, H; Nakayama, KI

    NATURE COMMUNICATIONS   14 ( 1 )   2131   2023.4   eISSN:2041-1723

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    Although several ribosomal protein paralogs are expressed in a tissue-specific manner, how these proteins affect translation and why they are required only in certain tissues have remained unclear. Here we show that RPL3L, a paralog of RPL3 specifically expressed in heart and skeletal muscle, influences translation elongation dynamics. Deficiency of RPL3L-containing ribosomes in RPL3L knockout male mice resulted in impaired cardiac contractility. Ribosome occupancy at mRNA codons was found to be altered in the RPL3L-deficient heart, and the changes were negatively correlated with those observed in myoblasts overexpressing RPL3L. RPL3L-containing ribosomes were less prone to collisions compared with RPL3-containing canonical ribosomes. Although the loss of RPL3L-containing ribosomes altered translation elongation dynamics for the entire transcriptome, its effects were most pronounced for transcripts related to cardiac muscle contraction and dilated cardiomyopathy, with the abundance of the encoded proteins being correspondingly decreased. Our results provide further insight into the mechanisms and physiological relevance of tissue-specific translational regulation.

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  • ZBP1 protects against mtDNA-induced myocardial inflammation in failing hearts. Invited Reviewed International journal

    Enzan N, Matsushima S, Ikeda S, Okabe K, Ishikita A, Yamamto T, Sada M, Miyake R, Tsutsui Y, Nishimura R, Toyohara T, Ikeda Y, Shojima Y, Miyamoto DH, Tadokoro T, Ikeda M, Abe K, Ide T, Kinugawa S, Tsutsui H

    Circ Res   2023.4

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  • Propensity-Matched Study of Early Cardiac Rehabilitation in Patients With Acute Decompensated Heart Failure

    Enzan, N; Matsushima, S; Kaku, H; Tohyama, T; Nezu, T; Higuchi, T; Nagatomi, Y; Fujino, T; Hashimoto, T; Ide, T; Tsutsui, H

    CIRCULATION-HEART FAILURE   16 ( 4 )   e010320   2023.4   ISSN:1941-3289 eISSN:1941-3297

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    Background: The impact of early implementation of cardiac rehabilitation (CR) in heart failure (HF) patients remains to be elucidated. This study sought to determine whether CR during HF hospitalization could improve prognostic outcomes in patients with acute decompensated HF. Methods: We analyzed patients with HF enrolled in the JROADHF (Japanese Registry of Acute Decompensated Heart Failure) registry, a retrospective, multicenter, nationwide registry of patients hospitalized for acute decompensated HF. Eligible patients were divided into 2 groups according to CR during hospitalization. The primary outcome was a composite of cardiovascular death or rehospitalization due to cardiovascular event after discharge. The secondary outcomes were cardiovascular death and cardiovascular event rehospitalization. Results: Out of 10 473 eligible patients, 3210 patients underwent CR. Propensity score matching yielded 2804 pairs. Mean age was 77±12 years and 3127 (55.8%) were male. During a mean follow-up of 2.8 years, the CR group had lower incidence rates of the composite outcome (291 versus 327 events per 1000 patient-years; rate ratio, 0.890 [95% CI, 0.830-0.954]; P=0.001) and rehospitalization due to cardiovascular event (262 versus 295 events per 1000 patient-years; rate ratio, 0.888 [95% CI, 0.825-0.956]; P=0.002) than the no CR group. In-hospital CR was associated with an improvement in Barthel index for activities of daily living (P=0.002). Patients with very low Barthel index at admission were benefited by CR in comparison with patients with independent Barthel index (very low; hazard ratio, 0.834 [95% CI, 0.742-0.938]: independent; hazard ratio, 0.985 [95% CI, 0.891-1.088]; P for interaction=0.035). Conclusions: CR implementation during hospitalization was associated with better long-term outcomes in patients with acute decompensated HF. These data support the need for a randomized, controlled, adequately powered trial to definitively test the role of early physical rehabilitation in hospitalized patients with HF.

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  • Nationwide Temporal Trends in Clinical Characteristics and Treatment of Dilated Cardiomyopathy From 2003 to 2013 in Japan-A Report From Clinical Personal Records

    Tsutsui, Y; Matsushima, S; Enzan, N; Noda, E; Shinohara, K; Hashimoto, T; Ide, T; Kinugawa, S; Tsutsui, H

    CIRCULATION JOURNAL   87 ( 4 )   500 - 507   2023.4   ISSN:1346-9843 eISSN:1347-4820

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    Background: Little is known about nationwide temporal trends in the clinical characteristics and treatment of dilated cardiomyopathy (DCM) in Japan. Methods and Results: We collected data regarding demographics, echocardiography, and treatment of DCM between 2003 to 2013 from Clinical Personal Records, a national registry organized by the Japanese Ministry of Health, Labour, and Welfare. Among the 40,794 DCM patients screened, 27,702 with left ventricular ejection fraction (LVEF) <50% and age ≥18 years were enrolled in this study and divided into 3 groups according to registration year: Group 1, 2003-2005 (10,006 patients); Group 2, 2006-2010 (11,252 patients); and Group 3, 2011-2013 (6,444 patients). Over time, there were decreases in age at registration (mean [±SD] 58.6±13.0 vs. 56.8±13.8 vs. 56.2±13.8 years; P<0.001) and LVEF (33.5±10.0% vs. 31.1±9.9% vs. 29.2± 9.7%; P<0.001), and an increase in patients with New York Heart Association Class III-IV (28.2% vs. 35.2% vs. 41.0%; P<0.001). The use of β-blockers (59.1% vs. 79.3% vs. 87.8%; P<0.001) and mineralocorticoid receptor antagonists (30.6% vs. 35.8% vs. 39.7%; P<0.001) increased over time. In multivariate analysis, male sex, systolic blood pressure, chronic kidney disease, hemoglobin, and registration year were positively associated, whereas age and LVEF were negatively associated, with β-blocker prescription. Conclusions: Although the clinical characteristics of DCM changed, the implementation of optimal medical therapy for DCM increased from 2003 to 2013 in Japan.

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  • Beneficial Effects of Dipeptidyl Peptidase-4 Inhibitors on Heart Failure With Preserved Ejection Fraction and Diabetes

    Enzan N., Matsushima S., Kaku H., Tohyama T., Nagata T., Ide T., Tsutsui H.

    JACC: Asia   3 ( 1 )   93 - 104   2023.2

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    Background: Dipeptidyl peptidase-4 (DPP-4) inhibitors have been shown to exert pleiotropic effects on heart failure (HF) in animal experiments. Objectives: This study sought to investigate the impact of DPP-4 inhibitors on HF patients with diabetes mellitus (DM). Methods: We analyzed hospitalized patients with HF and DM enrolled in the JROADHF (Japanese Registry Of Acute Decompensated Heart Failure) registry, a nationwide registry of acute decompensated HF. Primary exposure was the use of a DPP-4 inhibitor. The primary outcome was a composite of cardiovascular death or HF hospitalization during the median follow-up of 3.6 years according to left ventricular ejection fraction. Results: Out of 2,999 eligible patients, 1,130 had heart failure with preserved ejection fraction (HFpEF), 572 had heart failure with midrange ejection fraction (HFmrEF), and 1,297 had heart failure with reduced ejection fraction (HFrEF). In each cohort, 444, 232, and 574 patients received a DPP-4 inhibitor, respectively. A multivariable Cox regression model showed that DPP-4 inhibitor use was associated with a lower composite of cardiovascular death or HF hospitalization in HFpEF (HR: 0.69; 95% CI: 0.55-0.87; P = 0.002) but not in HFmrEF and HFrEF. Restricted cubic spline analysis demonstrated that DPP-4 inhibitors were beneficial in patients with higher left ventricular ejection fraction. In HFpEF cohort, propensity score matching yielded 263 pairs. DPP-4 inhibitor use was associated with a lower incidence rate of the composite of cardiovascular death or HF hospitalization (19.2 vs 25.9 events per 100 patient-years; rate ratio: 0.74; 95% CI: 0.57-0.97; P = 0.027) in matched patients. Conclusions: DPP-4 inhibitor use was associated with better long-term outcomes in HFpEF patients with DM.

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  • EFFECTIVENESS OF STATIN INTENSIVE THERAPY IN TYPE 2 DIABETES WITH HIGH VISIT-TO-VISIT BLOOD PRESSURE VARIABILITY

    Ikeda, S; Shinohara, K; Enzan, N; Matsushima, S; Tohyama, T; Funakoshi, K; Kishimoto, J; Itoh, H; Komuro, I; Tsutsui, H

    JOURNAL OF HYPERTENSION   41   E44 - E45   2023.1   ISSN:0263-6352 eISSN:1473-5598

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  • Histologic Diagnosis of Coronary Amyloidosis Using Percutaneous Transluminal Directional Atherectomy

    Yoshida, D; Hashimoto, T; Katsuki, M; Ishikita, A; Ishikawa, Y; Fujino, T; Shinohara, K; Matsushima, S; Kinugawa, S; Nakano, Y; Katsuki, S; Matoba, T; Hayashidani, S; Tsutsui, H

    CJC OPEN   5 ( 1 )   99 - 102   2023.1   ISSN:2589-790X

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  • 抗HLA抗体陽性患者に対する心臓移植周術期脱感作療法の経験

    藤野 剛雄, 山元 昇栄, 橋本 亨, 篠原 啓介, 松島 将士, 松永 章吾, 牛島 智基, 園田 拓道, 金萬 仁志, 豊沢 真代, 塩瀬 明, 絹川 真太郎

    移植   58 ( Supplement )   s197_1 - s197_1   2023   ISSN:05787947 eISSN:21880034

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    <p>心臓移植レシピエント候補の中でもpanel reactive antibody (PRA)高値の症例は、ドナー特異的抗HLA抗体(DSA)を生じやすく、移植後の拒絶反応リスクが高いことが想定される。</p><p>当院では、心臓移植を施行した61例のうち、4例(男性1例、女性3例)に周術期の脱感作療法を施行した。いずれもhigh PRAかつpreformed DSA陽性の症例であった。プロトコールとして、全例で移植術直前に血漿交換と免疫グロブリン投与を併用した。移植後の経過として、1例で急性期にgrade 1R/2の細胞性拒絶反応を認めたが、抗体関連拒絶反応を発症した症例はなく、心機能低下を来した症例もなかった。</p><p>当院でのhigh PRA症例に対する周術期脱感作療法は安全に施行でき、術後に問題となる拒絶反応も見られなかった。注意して長期経過を観察する必要がある。また、本邦では血漿交換や免疫グロブリン療法、さらにはリツキシマブといった治療は心臓移植における脱感作療法に対しては保険適応外であり、治療の有効性・必要性について今後も検証が必要である。</p>

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  • Immunomodulatory Cell Therapy Using αGalCer-Pulsed Dendritic Cells Ameliorates Heart Failure in a Murine Dilated Cardiomyopathy Model

    Ikeda, M; Ide, T; Matsushima, S; Ikeda, S; Okabe, K; Ishikita, A; Tadokoro, T; Sada, M; Abe, K; Sato, M; Hanada, A; Arai, S; Ohtani, K; Nonami, A; Mizuno, S; Morimoto, S; Motohashi, S; Akashi, K; Taniguchi, M; Tsutsui, H

    CIRCULATION-HEART FAILURE   15 ( 12 )   1125 - 1139   2022.12   ISSN:1941-3289 eISSN:1941-3297

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    Background: Dilated cardiomyopathy (DCM) is a life-threatening disease, resulting in refractory heart failure. An immune disorder underlies the pathophysiology associated with heart failure progression. Invariant natural killer T (iNKT) cell activation is a prospective therapeutic strategy for ischemic heart disease. However, its efficacy in nonischemic cardiomyopathy, such as DCM, remains to be elucidated, and the feasible modality for iNKT cell activation in humans is yet to be validated. Methods: Dendritic cells isolated from human volunteers were pulsed with α-galactosylceramide ex vivo, which were used as α-galactosylceramide-pulsed dendritic cells (αGCDCs). We treated DCM mice harboring mutated troponin TΔK210/ΔK210with αGCDCs and evaluated the efficacy of iNKT cell activation on heart failure in DCM mice. Furthermore, we investigated the molecular basis underlying its therapeutic effects in these mice and analyzed primary cardiac cells under iNKT cell-secreted cytokines. Results: The number of iNKT cells in the spleens of DCM mice was reduced compared with that in wild-type mice, whereas αGCDC treatment activated iNKT cells, prolonged survival of DCM mice, and prevented decline in the left ventricular ejection fraction for 4 weeks, accompanied by suppressed interstitial fibrosis. Mechanistically, αGCDC treatment suppressed TGF (transforming growth factor)-β signaling and expression of fibrotic genes and restored vasculature that was impaired in DCM hearts by upregulating angiopoietin 1 (Angpt1) expression. Consistently, IFNγ (interferon gamma) suppressed TGF-β-induced Smad2/3 signaling and the expression of fibrotic genes in cardiac fibroblasts and upregulated Angpt1 expression in cardiomyocytes via Stat1. Conclusions: Immunomodulatory cell therapy with αGCDCs is a novel therapeutic strategy for heart failure in DCM.

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  • Doxorubicin causes ferroptosis and cardiotoxicity by intercalating into mitochondrial DNA and disrupting Alas1-dependent heme synthesis

    Abe, K; Ikeda, M; Ide, T; Tadokoro, T; Miyamoto, HD; Furusawa, S; Tsutsui, Y; Miyake, R; Ishimaru, K; Watanabe, M; Matsushima, S; Koumura, T; Yamada, KI; Imai, H; Tsutsui, H

    SCIENCE SIGNALING   15 ( 758 )   eabn8017   2022.11   ISSN:1945-0877 eISSN:1937-9145

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    Clinical use of doxorubicin (DOX) is limited because of its cardiotoxicity, referred to as DOX-induced cardiomyopathy (DIC). Mitochondria-dependent ferroptosis, which is triggered by iron overload and excessive lipid peroxidation, plays a pivotal role in the progression of DIC. Here, we showed that DOX accumulated in mitochondria by intercalating into mitochondrial DNA (mtDNA), inducing ferroptosis in an mtDNA content-dependent manner. In addition, DOX disrupted heme synthesis by decreasing the abundance of 5'-aminolevulinate synthase 1 (Alas1), the rate-limiting enzyme in this process, thereby impairing iron utilization, resulting in iron overload and ferroptosis in mitochondria in cultured cardiomyocytes. Alas1 overexpression prevented this outcome. Administration of 5-aminolevulinic acid (5-ALA), the product of Alas1, to cultured cardiomyocytes and mice suppressed iron overload and lipid peroxidation, thereby preventing DOX-induced ferroptosis and DIC. Our findings reveal that the accumulation of DOX and iron in mitochondria cooperatively induces ferroptosis in cardiomyocytes and suggest that 5-ALA can be used as a potential therapeutic agent for DIC.

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  • Ethoxyquin is a Competent Radical-Trapping Antioxidant for Preventing Ferroptosis in Doxorubicin Cardiotoxicity

    Tadokoro, T; Ikeda, M; Abe, K; Ide, T; Miyamoto, HD; Furusawa, S; Ishimaru, K; Watanabe, M; Ishikita, A; Matsushima, S; Koumura, T; Yamada, K; Imai, H; Tsutsui, H

    JOURNAL OF CARDIOVASCULAR PHARMACOLOGY   80 ( 5 )   690 - 699   2022.11   ISSN:0160-2446 eISSN:1533-4023

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    Doxorubicin (DOX) is an effective anti-cancer agent for various malignancies. Nevertheless, it has a side effect of cardiotoxicity, referred to as doxorubicin-induced cardiomyopathy (DIC), that is associated with a poorer prognosis. This cardiotoxicity limits the clinical use of DOX as a therapeutic agent for malignancies. Recently, ferroptosis, a form of regulated cell death induced by the accumulation of lipid peroxides, has been recognized as a major pathophysiology of DIC. Ethoxyquin is a lipophilic antioxidant widely used for food preservation and thus may be a potential therapeutic drug for preventing DIC. However, the efficacy of ethoxyquin against ferroptosis and DIC remains to be fully elucidated. Here, we investigated the inhibitory action of ethoxyquin against GPx4-deficient ferroptosis and its therapeutic efficacy against DOX-induced cell death in cultured cardiomyocytes and cardiotoxicity in a murine model of DIC. In cultured cardiomyocytes, ethoxyquin treatment effectively prevented GPx4-deficient ferroptosis. Ethoxyquin also prevented DOX-induced cell death, accompanied by the suppression of malondialdehyde (MDA) and mitochondrial lipid peroxides, which were induced by DOX. Furthermore, ethoxyquin significantly prevented DOX-induced cell death without any suppression of caspase cleavages representing apoptosis. In DIC mice, ethoxyquin treatment ameliorated cardiac impairments, such as contractile dysfunction and myocardial atrophy, and lung congestion. Ethoxyquin also suppressed serum lactate dehydrogenase and creatine kinase activities, decreased the levels of lipid peroxides such as MDA and acrolein, inhibited cardiac fibrosis, and reduced TUNEL-positive cells in the hearts of DIC mice. Collectively, ethoxyquin is a competent antioxidant for preventing ferroptosis in DIC and can be its prospective therapeutic drug.

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  • Fulminant necrotizing eosinophilic myocarditis after COVID-19 vaccination survived with mechanical circulatory support

    Kimura, M; Hashimoto, T; Noda, E; Ishikawa, Y; Ishikita, A; Fujino, T; Matsushima, S; Ide, T; Kinugawa, S; Nagaoka, K; Ushijima, T; Shiose, A; Tsutsui, H

    ESC HEART FAILURE   9 ( 4 )   2732 - 2737   2022.8   ISSN:2055-5822

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    A 69-year-old man was hospitalized for heart failure 7 days after coronavirus disease 2019 (COVID-19) mRNA vaccination. Electrocardiography showed ST-segment elevation and echocardiography demonstrated severe left ventricular dysfunction. Venoarterial extracorporeal membrane oxygenation and Impella 5.0 were instituted because of cardiogenic shock and ventricular fibrillation. Endomyocardial biopsy demonstrated necrotizing eosinophilic myocarditis (NEM). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) PCR test was negative. He had no infection or history of new drug exposure. NEM was likely related to COVID-19 vaccination. He was administered 10 mg/kg of prednisolone following methylprednisolone pulse treatment (1000 mg/day for 3 days). Left ventricular function recovered and he was weaned from mechanical circulatory support (MCS). Follow-up endomyocardial biopsy showed no inflammatory cell infiltration. This is the first report of biopsy-proven NEM after COVID-19 vaccination survived with MCS and immunosuppression therapy. It is a rare condition but early, accurate diagnosis and early aggressive intervention can rescue patients.

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  • Iron Overload via Heme Degradation in the Endoplasmic Reticulum Triggers Ferroptosis in Myocardial Ischemia-Reperfusion Injury

    Miyamoto, HD; Ikeda, M; Ide, T; Tadokoro, T; Furusawa, S; Abe, K; Ishimaru, K; Enzan, N; Sada, M; Yamamoto, T; Matsushima, S; Koumura, T; Yamada, K; Imai, H; Tsutsui, H

    JACC-BASIC TO TRANSLATIONAL SCIENCE   7 ( 8 )   801 - 820   2022.8   ISSN:2452-302X

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    Ischemia-reperfusion (I/R) injury is a promising therapeutic target to improve clinical outcomes after acute myocardial infarction. Ferroptosis, triggered by iron overload and excessive lipid peroxides, is reportedly involved in I/R injury. However, its significance and mechanistic basis remain unclear. Here, we show that glutathione peroxidase 4 (GPx4), a key endogenous suppressor of ferroptosis, determines the susceptibility to myocardial I/R injury. Importantly, ferroptosis is a major mode of cell death in I/R injury, distinct from mitochondrial permeability transition (MPT)–driven necrosis. This suggests that the use of therapeutics targeting both modes is an effective strategy to further reduce the infarct size and thereby ameliorate cardiac remodeling after I/R injury. Furthermore, we demonstrate that heme oxygenase 1 up-regulation in response to hypoxia and hypoxia/reoxygenation degrades heme and thereby induces iron overload and ferroptosis in the endoplasmic reticulum (ER) of cardiomyocytes. Collectively, ferroptosis triggered by GPx4 reduction and iron overload in the ER is distinct from MPT-driven necrosis in both in vivo phenotype and in vitro mechanism for I/R injury. The use of therapeutics targeting ferroptosis in conjunction with cyclosporine A can be a promising strategy for I/R injury.

    DOI: 10.1016/j.jacbts.2022.03.012

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  • Home-based cardiac rehabilitation using information and communication technology for heart failure patients with frailty

    Nagatomi, Y; Ide, T; Higuchi, T; Nezu, T; Fujino, T; Tohyama, T; Nagata, T; Higo, T; Hashimoto, T; Matsushima, S; Shinohara, K; Yokoyama, T; Eguchi, A; Ogusu, A; Ikeda, M; Ishikawa, Y; Yamashita, F; Kinugawa, S; Tsutsui, H

    ESC HEART FAILURE   9 ( 4 )   2407 - 2418   2022.8   ISSN:2055-5822

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    Aims: Cardiac rehabilitation (CR) is an evidence-based, secondary preventive strategy that improves mortality and morbidity rates in patients with heart failure (HF). However, the implementation and continuation of CR remains unsatisfactory, particularly for outpatients with physical frailty. This study investigated the efficacy and safety of a comprehensive home-based cardiac rehabilitation (HBCR) programme that combines patient education, exercise guidance, and nutritional guidance using information and communication technology (ICT). Methods and results: This study was a single-centre, open-label, randomized, controlled trial. Between April 2020 and November 2020, 30 outpatients with chronic HF (New York Heart Association II–III) and physical frailty were enrolled. The control group (n = 15) continued with standard care, while the HBCR group (n = 15) also received comprehensive, individualized CR, including ICT-based exercise and nutrition guidance using ICT via a Fitbit® device for 3 months. The CR team communicated with each patient in HBCR group once a week via the application messaging tool and planned the training frequency and intensity of training individually for the next week according to each patient's symptoms and recorded pulse data during exercise. Dietitians conducted a nutritional assessment and then provided individual nutritional advice using the picture-posting function of the application. The primary outcome was the change in the 6 min walking distance (6MWD). The participants' mean age was 63.7 ± 10.1 years, 53% were male, and 87% had non-ischaemic heart disease. The observed change in the 6MWD was significantly greater in the HBCR group (52.1 ± 43.9 m vs. −4.3 ± 38.8 m; P < 0.001) at a 73% of adherence rate. There was no significant change in adverse events in either group. Conclusions: Our comprehensive HBCR programme using ICT for HF patients with physical frailty improved exercise tolerance and improved lower extremity muscle strength in our sample, suggesting management with individualized ICT-based programmes as a safe and effective approach. Considering the increasing number of HF patients with frailty worldwide, our approach provides an efficient method to keep patients engaged in physical activity in their daily life.

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  • Serial measurement of B-type natriuretic peptide and future cardiovascular events in patients with type 2 diabetes mellitus without known cardiovascular disease

    Ikeda, S; Shinohara, K; Enzan, N; Matsushima, S; Tohyama, T; Funakoshi, K; Kishimoto, J; Itoh, H; Komuro, I; Tsutsui, H

    INTERNATIONAL JOURNAL OF CARDIOLOGY   356   98 - 104   2022.6   ISSN:0167-5273 eISSN:1874-1754

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    Background: In patients with type 2 diabetes mellitus (T2DM) without known cardiovascular disease, the association between B-type natriuretic peptide (BNP) and cardiovascular events except for heart failure has not been elucidated. We aimed to investigate this association in high-risk T2DM patients. Methods: We analyzed the association between BNP and cardiovascular events, including coronary, cerebral, renal, and vascular events or cardiovascular death based on the single and serial measurement of BNP in T2DM patients with retinopathy and hyperlipidemia without known cardiovascular disease enrolled in the EMPATHY study. Results: Data from 4966 patients were analyzed for baseline BNP analysis. The median BNP value was 15.0 pg/mL. When analyzed in quartiles of baseline BNP (interquartile range 7.5–29.2 pg/mL), Q2, Q3, and Q4 were associated with cardiovascular events compared with Q1 (hazard ratio [HR]: Q2, 1.91 [P = 0.003]; Q3, 1.63 [P = 0.031]; Q4, 3.20 [P < 0.001]). The analysis of 12-month BNP showed similar associations. In serial BNP measurement, compared with low–low BNP group (baseline ≤35 pg/mL and 12-month ≤35 pg/mL), low–high BNP group as well as high–high BNP group was associated with cardiovascular events (HR: low–high, 2.05 [P = 0.004]; high–high, 2.07 [P = 0.001]) and non-renal cardiovascular events. High–low BNP group tended to be associated with non-renal cardiovascular events (HR vs low–low: 2.05 [P = 0.056]). Conclusions: BNP levels were associated with first cardiovascular events except for heart failure in T2DM patients with retinopathy and hyperlipidemia. Serial BNP measurement may be useful in further stratifying high-risk patients among this T2DM population.

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  • Yin and Yang of NADPH Oxidases in Myocardial Ischemia-Reperfusion

    Matsushima, S; Sadoshima, J

    ANTIOXIDANTS   11 ( 6 )   2022.6   ISSN:2076-3921 eISSN:2076-3921

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    Oxidative stress is critically involved in the pathophysiology of myocardial ischemicreperfusion (I/R) injury. NADPH oxidase (Nox) 2 and 4, major sources of reactive oxygen species (ROS) in cardiomyocytes, are upregulated in response to I/R. Suppression of Nox‐derived ROS prevents mitochondrial dysfunction and endoplasmic reticulum (ER) stress, leading to attenuation of myocardial I/R injury. However, minimal levels of ROS by either Nox2 or Nox4 are required for energy metabolism during I/R in the heart, preserving hypoxia‐inducible factor‐1α (HIF‐1α) and peroxisome proliferator‐activated receptor‐α (PPARα) levels. Furthermore, extreme suppression of Nox activity induces reductive stress, leading to paradoxical increases in ROS levels. Nox4 has distinct roles in organelles such as mitochondria, ER, and ER‐mitochondria contact sites (MAMs). Mitochondrial Nox4 exerts a detrimental effect, causing ROS‐induced mitochondrial dysfunction during I/R, whereas Nox4 in the ER and MAMs is potentially protective against I/R injury through regulation of autophagy and MAM function, respectively. Although Nox isoforms are potential therapeutic targets for I/R injury, to maximize the effect of intervention, it is likely important to optimize the ROS level and selectively inhibit Nox4 in mitochondria. Here, we discuss the ‘Yin and Yang’ functions of Nox isoforms during myocardial I/R.

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  • The use of angiotensin II receptor blocker is associated with greater recovery of cardiac function than angiotensin-converting enzyme inhibitor in dilated cardiomyopathy

    Enzan, N; Matsushima, S; Ide, T; Tohyama, T; Funakoshi, K; Higo, T; Tsutsui, H

    ESC HEART FAILURE   9 ( 2 )   1175 - 1185   2022.4   ISSN:2055-5822

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    Aims: Angiotensin-converting enzyme inhibitors (ACEis) or angiotensin II receptor blockers (ARBs) have been shown to be associated with recovery of cardiac function in patients with dilated cardiomyopathy (DCM). The aim of this study was to assess comparative effectiveness of ACEis vs. ARBs on recovery of left ventricular ejection fraction (LVEF) among patients with DCM. Methods and results: We analysed the clinical personal records of DCM, a national database of the Japanese Ministry of Health, Labour and Welfare, from 2003 to 2014. Patients with LVEF < 40% and on either ACEis or ARBs were included. Eligible patients were divided into two groups according to the use of ACEis or ARBs. A one-to-one propensity case-matched analysis was used. The primary outcome was defined as LVEF ≥ 40% at 3 years of follow-up. Out of 4618 eligible patients, 2238 patients received ACEis and 2380 patients received ARBs. Propensity score matching yielded 1341 pairs. Mean age was 56.0 years, 2041 (76.1%) were male, median duration of heart failure was 1 year, and mean LVEF was 27.6%. The primary outcome was observed more frequently in ARB group than in ACEi group (59.8% vs. 54.1%; odds ratio 1.26; 95% confidence interval 1.08–1.47; P = 0.003). The per-protocol analysis showed similar results (62.0% vs. 54.0%; odds ratio 1.39; 95% confidence interval 1.17–1.66; P < 0.001). The change in LVEF from baseline to 3 years of follow-up was greater in ARB group than in ACEi group (15.8 ± 0.4% vs. 14.0 ± 0.4%, P = 0.003). The subgroup analysis showed that this effect was observed independently of systolic blood pressure, heart rate, LVEF, chronic kidney disease, and concomitant use of beta-blockers and mineralocorticoid receptor antagonists. Conclusions: The use of ARBs was associated with LVEF recovery more frequently than ACEis among patients with DCM and reduced LVEF.

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  • Electrocardiographic Diagnosis of Hypertrophic Cardiomyopathy in the Pre- and Post-Diagnostic Phases in Children and Adolescents

    Yoshinaga, M; Horigome, H; Ayusawa, M; Yasuda, K; Kogaki, S; Doi, S; Tateno, S; Ohta, K; Hokosaki, T; Nishihara, E; Iwamoto, M; Sumitomo, N; Ushinohama, H; Izumida, N; Tauchi, N; Kato, Y; Kato, T; Chisaka, T; Higaki, T; Yoneyama, T; Abe, K; Nozaki, Y; Komori, A; Kawai, S; Ninomiya, Y; Tanaka, Y; Nuruki, N; Sonoda, M; Ueno, K; Hazeki, D; Nomura, Y; Sato, S; Hirono, K; Hosokawa, S; Takechi, F; Ishikawa, Y; Hata, T; Ichida, F; Ohno, S; Makita, N; Horie, M; Matsushima, S; Tsutsui, H; Ogata, H; Takahashi, H; Nagashima, M

    CIRCULATION JOURNAL   86 ( 1 )   118 - +   2022.1   ISSN:1346-9843 eISSN:1347-4820

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    Background: The usefulness of electrocardiographic (ECG) voltage criteria for diagnosing hypertrophic cardiomyopathy (HCM) in pediatric patients is poorly defined. Methods and Results: ECGs at the 1st grade (mean [±SD] age 6.6±0.3 years) were available for 11 patients diagnosed with HCM at around the 7th grade (13.2±0.3 years). ECGs were available for another 64 patients diagnosed with HCM in the 1st (n=15), 7th (n=32), and 10th (n=17) grades. Fifty-one voltage criteria were developed by grade and sex using 62,841 ECGs from the general population. Voltage criteria were set at the 99.95th percentile (1/2,000) point based on the estimated prevalence of childhood HCM (2.9 per 100,000 [1/34,483]) to decrease false negatives. Conventional criteria were from guidelines for school-aged children in Japan. Of 11 patients before diagnosis, 2 satisfied conventional criteria in 1st grade; 5 (56%) of the remaining 9 patients fulfilled 2 voltage criteria (R wave in limb-lead I [RI]+S wave in lead V3 [SV3] and R wave in lead V3 [RV3]+SV3). Robustness analysis for sensitivity showed RV3+SV3 was superior to RI+SV3. For all patients after diagnosis, RI+SV4 was the main candidate. However, conventional criteria were more useful than voltage criteria. Conclusions: Early HCM prediction was possible using RV3+SV3 in >50% of patients in 1st grade. Voltage criteria may help diagnose prediagnostic or early HCM, and prevent tragic accidents, although further prospective studies are required.

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  • GFAT2 Mediates Cardiac Hypertrophy through HBP-O-GlcNAcylation-Akt Pathway. Reviewed International journal

    Ishikita A, Matsushima S, Ikeda S, Okabe K, Nishimura R, Tadokoro T, Enzan N, Yamamoto T, Sada M, Tsutsui Y, Miyake R, Ikeda M, Ide T, Kinugawa S, Tsutsui H

    iScience. 24(12):103517, 2021   2021.6

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  • Clinical Characteristics and Contemporary Management of Patients With Cardiomyopathies in Japan - Report From a National Registry of Clinical Personal Records Invited Reviewed International journal

    Enzan N, Matsushima S, Ide T, Kaku H, Tohyama T, Funakoshi K, Higo T, Tsutsui H; Research Group of Idiopathic Cardiomyopathy

    Circ Rep   3 ( 3 )   142   2021.2

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    DOI: 10.1253/circrep.CR-21-0001.

  • Cardiac-specific loss of mitoNEET expression is linked with age-related heart failure Invited Reviewed International journal

    Furihata T, Takada S, Kakutani N, Maekawa S, Tsuda M, Matsumoto J, Mizushima W, Fukushima A, Yokota T, Enzan N, Matsushima S, Handa H, Fumoto Y, Nio-Kobayashi J, Iwanaga T, Tanaka S, Tsutsui H, Sabe H, Kinugawa S.

    Commun Biol.   4 ( 1 )   138   2021.1

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    DOI: 10.1038/s42003-021-01675-4.

  • Heart Rate Reduction with Ivabradine Prevents Cardiac Rupture after Myocardial Infarction in Mice. Reviewed International journal

    Ikeda M, Ide T, Furusawa S, Ishimaru K, Tadokoro T, Miyamoto HD, Ikeda S, Okabe K, Ishikita A, Abe K, Matsushima S, Tsutsui H.

    Cardiovasc Drugs Ther.   36 ( 2 )   257 - 262   2021.1   ISSN:0920-3206 eISSN:1573-7241

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    DOI: 10.1007/s10557-020-07123-5

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  • Systemic oxidative stress is associated with lower aerobic capacity and impaired skeletal muscle energy metabolism in heart failure patients Invited Reviewed International journal

    Yokota T, Kinugawa S, Hirabayashi K, Yamato M, Takada S, Suga T, Nakano I, Fukushima A, Matsushima S, Okita K, Tsutsui H.

    Sci Rep   11 ( 1 )   2272   2021.1

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    DOI: 10.1038/s41598-021-81736-0

  • Mitochondria-dependent ferroptosis plays a pivotal role in doxorubicin cardiotoxicity Reviewed

    Tomonori Tadokoro, Masataka Ikeda, Tomomi Ide, Hiroko Deguchi, Soichiro Ikeda, Kosuke Okabe, Akihito Ishikita, Shouji Matsushima, Tomoko Koumura, Ken Ichi Yamada, Hirotaka Imai, Hiroyuki Tsutsui

    JCI Insight   5 ( 9 )   2020.5

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    DOI: 10.1172/jci.insight.132747

  • DPP (dipeptidyl peptidase)-4 inhibitor attenuates ANG II (angiotensin II)–induced cardiac hypertrophy via GLP (glucagon-like peptide)-1–dependent suppression of NOx (nicotinamide adenine dinucleotide phosphate oxidase) 4-HDAC (histone deacetylase) 4 pathway Reviewed

    991 - 1001   2020.4

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    —Nox4 (NADPH [Nicotinamide adenine dinucleotide phosphate] oxidase 4) is a major source of oxidative stress and is intimately involved in cardiac hypertrophy. DPP (Dipeptidyl peptidase)-4 inhibitor has been reported to regulate Nox4 expression in adipose tissues. However, its effects on Nox4 in cardiac hypertrophy are still unclear. We investigated whether DPP-4 inhibitor could ameliorate cardiac hypertrophy by regulating Nox4 and its downstream targets. Ang II (Angiotensin II; 1.44 mg/kg per day) or saline was continuously infused into C57BL/6J mice with or without teneligliptin (a DPP-4 inhibitor, 30 mg/kg per day) in the drinking water for 1 week. Teneligliptin significantly suppressed plasma DPP-4 activity without any significant changing aortic blood pressure or metabolic parameters such as blood glucose and insulin levels. It attenuated Ang II–induced increases in left ventricular wall thickness and the ratio of heart weight to body weight. It also significantly suppressed Ang II–induced increases in Nox4 mRNA, 4-hydroxy-2-nonenal, and phosphorylation of HDAC4 (histone deacetylase 4), a downstream target of Nox4 and a crucial suppressor of cardiac hypertrophy, in the heart. Exendin-3 (150 pmol/kg per minute), a GLP-1 (glucagon-like peptide 1) receptor antagonist, abrogated these inhibitory effects of teneligliptin on Nox4, 4-hydroxy-2-nonenal, phosphorylation of HDAC4, and cardiac hypertrophy. In cultured neonatal cardiomyocytes, exendin-4 (100 nmol/L, 24 hours), a GLP-1 receptor agonist, ameliorated Ang II–induced cardiomyocyte hypertrophy and decreased in Nox4, 4-hydroxy-2-nonenal, and phosphorylation of HDAC4. Furthermore, exendin-4 prevented Ang II–induced decrease in nuclear HDAC4 in cardiomyocytes. In conclusion, GLP-1 receptor stimulation by DPP-4 inhibitor can attenuate Ang II–induced cardiac hypertrophy by suppressing of the Nox4-HDAC4 axis in cardiomyocytes.

    DOI: 10.1161/HYPERTENSIONAHA.119.14400

  • Spironolactone use is associated with improved outcomes in heart failure with mid-range ejection fraction Reviewed

    Nobuyuki Enzan, Shouji Matsushima, Tomomi Ide, Hidetaka Kaku, Taiki Higo, Miyuki Tsuchihashi-Makaya, Hiroyuki Tsutsui

    ESC Heart Failure   7 ( 1 )   339 - 347   2020.2

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    DOI: 10.1002/ehf2.12571

  • Left ventricular noncompaction with multiple thrombi in apical aneurysm Reviewed

    Daisuke Yakabe, Shouji Matsushima, Saori Uchino, Kisho Ohtani, Tomomi Ide, Taiki Higo, Hiroyuki Tsutsui

    Internal Medicine   59 ( 3 )   377 - 381   2020.2

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    DOI: 10.2169/internalmedicine.3489-19

  • Roxadustat markedly reduces myocardial ischemia reperfusion injury in mice Reviewed

    Hiroko Deguchi, Masataka Ikeda, Tomomi Ide, Tomonori Tadokoro, Soichiro Ikeda, Kosuke Okabe, Akihito Ishikita, Keita Saku, Shouji Matsushima, Hiroyuki Tsutsui

    Circulation Journal   84 ( 6 )   1028 - 1033   2020

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  • Impact of hospital practice factors on mortality in patients hospitalized for heart failure in Japan ― an analysis of a large number of health records from a nationwide claims-based database, the JROAD-DPC ― Reviewed

    84 ( 5 )   742 - 753   2020

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    Background: An inverse relationship exists between hospital case volume and mortality in patients with heart failure (HF). However, hospital performance factors associated with mortality in HF patients have not been examined. We aimed to identify these using exploratory factor analysis and assess the relationship between these factors and 7-day, 30-day, and in-hospital mortality among HF patients in Japan. Methods and Results: We analyzed the records of 198,861 patients admitted to 683 certified hospitals of the Japanese Circulation Society between 2012 and 2014. Records were obtained from the nationwide database of the Japanese Registry Of All cardiac and vascular Diseases-Diagnostic Procedure Combination (JROAD-DPC). Using exploratory factor analysis, 90 hospital survey items were grouped into 5 factors, according to their collinearity: “Interventional cardiology”, “Cardiovascular surgery”, “Pediatric cardiology”, “Electrophysiology” and “Cardiac rehabilitation”. Multivariable logistic regression analysis was performed to determine the association between these factors and mortality. The 30-day mortality was 8.0%. Multivariable logistic regression analysis showed the “Pediatric cardiology” (odds ratio (OR) 0.677, 95% confidence interval [CI]: 0.628–0.729, P<0.0001), “Electrophysiology” (OR 0.876, 95% CI: 0.832–0.923, P<0.0001), and “Cardiac rehabilitation” (OR 0.832, 95% CI: 0.792–0.873, P<0.0001) factors were associated with lower mortality. In contrast, “Interventional cardiology” (OR 1.167, 95% CI: 1.070–1.272, P<0.0001) was associated with higher mortality. Conclusions: Hospital factors, including various cardiovascular therapeutic practices, may be associated with the early death of HF patients.

    DOI: 10.1253/circj.CJ-19-0759

  • Blockade of L-type Ca2+ channel attenuates doxorubicin-induced cardiomyopathy via suppression of CaMKII-NF-κB pathway Reviewed

    9 ( 1 )   2019.12

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    Ca2+/calmodulin-dependent protein kinase II (CaMKII) and nuclear factor-kappa B (NF-κB) play crucial roles in pathogenesis of doxorubicin (DOX)-induced cardiomyopathy. Their activities are regulated by intracellular Ca2+. We hypothesized that blockade of L-type Ca2+ channel (LTCC) could attenuate DOX-induced cardiomyopathy by regulating CaMKII and NF-κB. DOX activated CaMKII and NF-κB through their phosphorylation and increased cleaved caspase 3 in cardiomyocytes. Pharmacological blockade or gene knockdown of LTCC by nifedipine or small interfering RNA, respectively, suppressed DOX-induced phosphorylation of CaMKII and NF-κB and apoptosis in cardiomyocytes, accompanied by decreasing intracellular Ca2+ concentration. Autocamtide 2-related inhibitory peptide (AIP), a selective CaMKII inhibitor, inhibited DOX-induced phosphorylation of NF-κB and cardiomyocyte apoptosis. Inhibition of NF-κB activity by ammonium pyrrolidinedithiocarbamate (PDTC) suppressed DOX-induced cardiomyocyte apoptosis. DOX-treatment (18 mg/kg via intravenous 3 injections over 1 week) increased phosphorylation of CaMKII and NF-κB in mouse hearts. Nifedipine (10 mg/kg/day) significantly suppressed DOX-induced phosphorylation of CaMKII and NF-κB and cardiomyocyte injury and apoptosis in mouse hearts. Moreover, it attenuated DOX-induced left ventricular dysfunction and dilatation. Our findings suggest that blockade of LTCC attenuates DOX-induced cardiomyocyte apoptosis via suppressing intracellular Ca2+ elevation and activation of CaMKII-NF-κB pathway. LTCC blockers might be potential therapeutic agents against DOX-induced cardiomyopathy.

    DOI: 10.1038/s41598-019-46367-6

  • Left Ventricular Noncompaction with Multiple Thrombi in Apical Aneurysm. Reviewed International journal

    Yakabe D, Matsushima S, Uchino S, Ohtani K, Ide T, Higo T, Tsutsui H

    2019.8

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  • Blockade of L-type Ca2+ channel attenuates doxorubicin-induced cardiomyopathy via suppression of CaMKII-NF-κB pathway. Reviewed International journal

    2019.6

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  • Predicting Survival in Acute Decompensated Heart Failure with the Simple Risk Score: A2B Score. Reviewed International journal

    Nakada Y, Kawakami R, Matsushima S, Ide T, Kanaoka K, Ueda T, Ishihara S, Nishida T, Onoue K, Soeda T, Okayama S, Watanabe M, Okura H, Tsuchihashi-Makaya M, Tsutsui H, Saito Y.

    Circ J   2019.6

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  • Electrocardiographic Left Ventricular Hypertrophy is Independently Associated with Better Long-Term Outcomes in Dilated Cardiomyopathy Patients. Reviewed International journal

    Matsushima S, Kaku H, Enzan N, Ide T, Higo T, Tsuchihashi-Makaya M, Tsutsui H

    Circ Rep   2019.6

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  • Simple risk score to predict survival in acute decompensated heart failure A2B score Reviewed

    Yasuki Nakada, Rika Kawakami, Shouji Matsushima, Tomomi Ide, Koshiro Kanaoka, Tomoya Ueda, Satomi Ishihara, Taku Nishida, Kenji Onoue, Tsunenari Soeda, Satoshi Okayama, Makoto Watanabe, Hiroyuki Okura, Miyuki Tsuchihashi-Makaya, Hiroyuki Tsutsui, Yoshihiko Saito

    Circulation Journal   83 ( 5 )   1019 - 1024   2019

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    DOI: 10.1253/circj.CJ-18-1116

  • Pioglitazone improves whole-body aerobic capacity and skeletal muscle energy metabolism in patients with metabolic syndrome Reviewed

    Takashi Yokota, Shintaro Kinugawa, Kagami Hirabayashi, Tadashi Suga, Shingo Takada, Masashi Omokawa, Tomoyasu Kadoguchi, Masashige Takahashi, Arata Fukushima, Shouji Matsushima, Mayumi Yamato, Koichi Okita, Hiroyuki Tsutsui

    Journal of Diabetes Investigation   8 ( 4 )   535 - 541   2017.7

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    DOI: 10.1111/jdi.12606

  • Pioglitazone improves whole-body aerobic capacity and skeletal muscle energy metabolism in patients with metabolic syndrome. Reviewed International journal

    Yokota T, Kinugawa S, Hirabayashi K, Suga T, Takada S, Omokawa M, Kadoguchi T, Takahashi M, Fukushima A, Matsushima S, Yamato M, Okita K, Tsutsui H.

    J Diabetes Investig   2017.6

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  • The novel heart-specific RING finger protein 207 is involved in energy metabolism in cardiomyocytes Reviewed

    Wataru Mizushima, Hidehisa Takahashi, Masashi Watanabe, Shintaro Kinugawa, Shouji Matsushima, Shingo Takada, Takashi Yokota, Takaaki Furihata, Junichi Matsumoto, Masaya Tsuda, Ikuru Chiba, Shun Nagashima, Shigeru Yanagi, Masaki Matsumoto, Keiichi I. Nakayama, Hiroyuki Tsutsui, Shigetsugu Hatakeyama

    Journal of Molecular and Cellular Cardiology   100   43 - 53   2016.11

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    DOI: 10.1016/j.yjmcc.2016.09.013

  • The novel heart-specific RING finger protein 207 is involved in energy metabolism in cardiomyocytes. Reviewed International journal

    J Mol Cell Cardiol   100:   43 - 53   2016.10

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  • Dipeptidyl peptidase-4 inhibitor improved exercise capacity and mitochondrial biogenesis in mice with heart failure via activation of glucagon-like peptide-1 receptor signalling Reviewed

    Shingo Takada, Yoshihiro Masaki, Shintaro Kinugawa, Junichi Matsumoto, Takaaki Furihata, Wataru Mizushima, Tomoyasu Kadoguchi, Arata Fukushima, Tsuneaki Homma, Masashige Takahashi, Shinichi Harashima, Shouji Matsushima, Takashi Yokota, Shinya Tanaka, Koichi Okita, Hiroyuki Tsutsui

    Cardiovascular research   111 ( 4 )   338 - 347   2016.9

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    DOI: 10.1093/cvr/cvw182

  • Tyrosine kinase FYN negatively regulates NOX4 in cardiac remodeling Reviewed

    Shouji Matsushima, Junya Kuroda, Peiyong Zhai, Tong Liu, Shohei Ikeda, Narayani Nagarajan, Shin Ichi Oka, Takashi Yokota, Shintaro Kinugawa, Chiao Po Hsu, Hong Li, Hiroyuki Tsutsui, Junichi Sadoshima

    Journal of Clinical Investigation   126 ( 9 )   3403 - 3416   2016.9

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    DOI: 10.1172/JCI85624

  • Tyrosine kinase FYN negatively regulates NOX4 in cardiac remodeling. Reviewed International journal

    Journal of Clinical Investigation   126 ( 9 )   3403 - 34-16   2016.9

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  • Incidental focal myocardial 18F-FDG uptake indicating asymptomatic coronary artery disease Reviewed

    Tadao Aikawa, Masanao Naya, Osamu Manabe, Masahiko Obara, Shouji Matsushima, Nagara Tamaki, Hiroyuki Tsutsui

    Journal of Nuclear Cardiology   23 ( 3 )   596 - 598   2016.6

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    DOI: 10.1007/s12350-015-0258-5

  • The experimental model of transition from compensated cardiac hypertrophy to failure created by transverse aortic constriction in mice Reviewed

    Takaaki Furihata, Shintaro Kinugawa, Shingo Takada, Arata Fukushima, Masashige Takahashi, Tsuneaki Homma, Yoshihiro Masaki, Masaya Tsuda, Junichi Matsumoto, Wataru Mizushima, Shouji Matsushima, Takashi Yokota, Hiroyuki Tsutsui

    IJC Heart and Vasculature   11   24 - 28   2016.6

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    DOI: 10.1016/j.ijcha.2016.03.007

  • Direct renin inhibitor ameliorates insulin resistance by improving insulin signaling and oxidative stress in the skeletal muscle from post-infarct heart failure in mice Reviewed

    Arata Fukushima, Shintaro Kinugawa, Shingo Takada, Junichi Matsumoto, Takaaki Furihata, Wataru Mizushima, Masaya Tsuda, Takashi Yokota, Shouji Matsushima, Koichi Okita, Hiroyuki Tsutsui

    European Journal of Pharmacology   779   147 - 156   2016.5

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    DOI: 10.1016/j.ejphar.2016.03.022

  • Poldip2 negatively regulates matrix synthesis at focal adhesions Reviewed

    Shouji Matsushima, Daniela Zablocki, Hiroyuki Tsutsui, Junichi Sadoshima

    Journal of Molecular and Cellular Cardiology   94   10 - 12   2016.5

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    DOI: 10.1016/j.yjmcc.2016.03.001

  • Sesamin prevents decline in exercise capacity and impairment of skeletal muscle mitochondrial function in mice with high-fat diet-induced diabetes Reviewed

    Shingo Takada, Shintaro Kinugawa, Shouji Matsushima, Daisuke Takemoto, Takaaki Furihata, Wataru Mizushima, Arata Fukushima, Takashi Yokota, Yoshiko Ono, Hiroshi Shibata, Koichi Okita, Hiroyuki Tsutsui

    Experimental Physiology   100 ( 11 )   1319 - 1330   2015.11

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    DOI: 10.1113/EP085251

  • MIR-206 Mediates YAP-Induced Cardiac Hypertrophy and Survival Reviewed

    Yanfei Yang, Dominic P. Del Re, Noritsugu Nakano, Sebastiano Sciarretta, Peiyong Zhai, Jiyeon Park, Danish Sayed, Akihiro Shirakabe, Shoji Matsushima, Yongkyu Park, Bin Tian, Maha Abdellatif, Junichi Sadoshima

    Circulation research   117 ( 10 )   891 - 904   2015.10

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    DOI: 10.1161/CIRCRESAHA.115.306624

  • Low-intensity exercise under ischemic conditions enhances metabolic stress in patients with heart failure Reviewed

    Masashige Takahashi, Shintaro Kinugawa, Shingo Takada, Kagami Hirabayashi, Takashi Yokota, Shouji Matsushima, Akimichi Saito, Koichi Okita, Hiroyuki Tsutsui

    International Journal of Cardiology   201   142 - 144   2015.10

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    DOI: 10.1016/j.ijcard.2015.08.022

  • Skeletal muscle abnormalities in heart failure Reviewed

    Shintaro Kinugawa, Shingo Takada, Shouji Matsushima, Koichi Okita, Hiroyuki Tsutsui

    International heart journal   56 ( 5 )   475 - 484   2015.9

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    DOI: 10.1536/ihj.15-108

  • AST-120 ameliorates lowered exercise capacity and mitochondrial biogenesis in the skeletal muscle from mice with chronic kidney disease via reducing oxidative stress Reviewed

    Mikito Nishikawa, Naoki Ishimori, Shingo Takada, Akimichi Saito, Tomoyasu Kadoguchi, Takaaki Furihata, Arata Fukushima, Shouji Matsushima, Takashi Yokota, Shintaro Kinugawa, Hiroyuki Tsutsui

    Nephrology Dialysis Transplantation   30 ( 6 )   934 - 942   2015.6

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    DOI: 10.1093/ndt/gfv103

  • Serum brain-derived neurotropic factor level predicts adverse clinical outcomes in patients with heart failure Reviewed

    Arata Fukushima, Shintaro Kinugawa, Tsuneaki Homma, Yoshihiro Masaki, Takaaki Furihata, Takashi Yokota, Shouji Matsushima, Shingo Takada, Tomoyasu Kadoguchi, Koji Oba, Koichi Okita, Hiroyuki Tsutsui

    Journal of Cardiac Failure   21 ( 4 )   300 - 306   2015.4

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    DOI: 10.1016/j.cardfail.2015.01.003

  • Angiotensin II can directly induce mitochondrial dysfunction, decrease oxidative fibre number and induce atrophy in mouse hindlimb skeletal muscle Reviewed

    Tomoyasu Kadoguchi, Shintaro Kinugawa, Shingo Takada, Arata Fukushima, Takaaki Furihata, Tsuneaki Homma, Yoshihiro Masaki, Wataru Mizushima, Mikito Nishikawa, Masashige Takahashi, Takashi Yokota, Shouji Matsushima, Koichi Okita, Hiroyuki Tsutsui

    Experimental Physiology   100 ( 3 )   312 - 322   2015.3

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    DOI: 10.1113/expphysiol.2014.084095

  • The role of sirtuins in cardiac disease Reviewed

    Shouji Matsushima, Junichi Sadoshima

    American Journal of Physiology - Heart and Circulatory Physiology   309 ( 9 )   H1375 - H1389   2015

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    DOI: 10.1152/ajpheart.00053.2015

  • Combinations of olmesartan and a calciumchannel blocker or a diuretic inelderly hypertensive patients A randomized, controlled trial Reviewed

    Toshio Ogihara, Takao Saruta, Hiromi Rakugi, Ikuo Saito, Kazuaki Shimamoto, Hiroaki Matsuoka, Kazuyuki Shimada, Sadayoshi Ito, Masatsugu Horiuchi, Tsutomu Imaizumi, Shuichi Takishita, Jitsuo Higaki, Shigehiro Katayama, Genjiroh Kimura, Satoshi Umemura, Nobuyuki Ura, Koichi Hayashi, Masato Odawara, Norio Tanahashi, Toshihiko Ishimitsu, Naoki Kashihara, Satoshi Morita, Satoshi Teramukai, T. Anno, S. Aoyama, N. Arima, Y. Bando, Y. Dohi, H. Fujioka, M. Fukuda, S. Fukuda, M. Fukuta, Y. Futamura, Y. Hirakawa, K. Imaeda, H. Imai, A. Imamura, M. Ito, O. Ito, T. Ito, T. Iwa, J. Izumi, Y. Kaga, K. Kanematsu, Y. Kato, Y. Kawata, T. Kitamura, K. Kobayashi, M. Koyasu, S. Kuwabara, M. Kuzuya, M. Maekawa, H. Mihara, F. Mitsuguchi, T. Murohara, T. Narita, K. Negi, Y. Numaguchi, T. Ohya, N. Okayama, K. Okuma, N. Ozaki, N. Ozeki, K. Sato, T. Sawada, Y. Seino, M. Suezawa, T. Suzuki, Y. Suzuki, N. Takahashi, R. Takahashi, N. Tanaka, Y. Wakida, H. Watanuki, M. Watarai, K. Yamada, S. Yamashita, M. Yoshikane, M. Goto, Y. Ishida, H. Kimura, K. Takahashi, N. Yashima, Y. Abe, S. Fujiwara, H. Higashino, M. Kaizuka, O. Minami, Y. Ogiu, T. Osanai, T. Sasaki, A. Sato, K. Sugimoto, H. Takahashi, K. Tanabe, D. Azuma, C. Ibuki, H. Inoya, T. Iyo, M. Kusaka, M. Ogawa, Y. Okubo, H. Rinno, M. Sano, T. Shishikura, H. Takahara, M. Takano, T. Takemura, S. Yamamoto, Y. Yonemitsu, M. Hasui, T. Honda, M. Igase, S. Kimoto, K. Kohno, S. Kondo, T. Oonishi, H. Saeki, T. Sunayama, H. Takahashi, C. Wakisaka, H. Watanabe, K. Watanabe, Y. Iwahori, Alan H.C. Lau, S. Ando, H. Eguchi, M. Fujino, J. Fukui, T. Gondo, S. Hatakeyama, K. Hirano, Y. Hirooka, H. Ikeda, T. Inou, T. Jinnouchi, T. Kadokami, H. Kai, H. Kameo, M. Kaneyuki, A. Katoh, H. Kishikawa, H. Koiwaya, K. Kusaba, S. Maeda, S. Maki, M. Matsumoto, T. Matsumoto, J. Matsumura, S. Matsuo, H. Meno, S. Miki, J. Miyagi, T. Miyauchi, S. Mori, M. Nagashima, S. Nagata, R. Nakamura, T. Nakamura, H. Niiyama, K. Noda, M. Nohara, Y. Ohta, I. Onitsuka, T. Otonari, S. Ouma, T. Sakisaka, K. Saku, K. Sasaki, S. Sasaki, Y. Sawayama, M. Shihara, K. Shiota, K. Shirakawa, Y. Tachikawa, S. Takemura, T. Takeuchi, M. Tanabe, M. Tanaka, H. Tashiro, M. Tatsukawa, T. Tsuchihashi, T. Tsuiki, T. Tsutsui, Y. Uehara, H. Umei, T. Yamada, J. Yamagata, T. Ajihara, K. Hagiwara, S. Imamura, M. Inoue, I. Konno, K. Konta, Y. Kubota, H. Kumakawa, T. Kuwana, H. Mitsuhashi, Y. Miyazaki, J. Nagashima, M. Nambu, T. Nishimaki, M. Sato, Y. Taneda, T. Tezuka, T. Yabuki, F. Ando, Y. Fuwa, S. Umeda, O. Araki, Y. Furushima, Y. Hattori, H. Hirabayashi, M. Horigome, J. Hoshino, C. Iguchi, H. Inamura, H. Kawauchi, S. Kogure, H. Kubo, F. Naganuma, T. Nagao, T. Nagao, T. Nagata, H. Nakashima, Y. Shimizu, H. Shoda, M. Tachibana, K. Yabe, R. Kuwashima, R. Mouri, T. Murakami, H. Muraoka, S. Nomura, F. Okuno, N. Sasaki, R. Sasaki, T. Satoh, M. Shirataki, H. Sugino, H. Takahashi, H. Takemoto, J. Ashihara, T. Betsuyaku, T. Fujita, T. Haga, M. Hayashi, Y. Hayashi, K. Hirasawa, Y. Ishii, R. Ishimoto, T. Komakine, M. Kyuma, I. Maeda, H. Matsuda, T. Matsuki, T. Matsumoto, T. Mito, M. Mizutani, H. Morimoto, S. Natori, T. Nishimiya, M. Nishimura, H. Oimatsu, H. Ooiwa, S. Saitoh, Y. Sasagawa, T. Segawa, H. Shuke, K. Sotozono, S. Takagi, S. Tanaka, M. Tashi, T. Tsubokura, Y. Ueno, K. Urabe, K. Yamauchi, H. Yoshida, M. Amano, Y. Hiroumi, K. Iiyama, H. Kido, A. Kosaka, A. Nogami, M. Okada, M. Shigenobu, R. Shigeta, S. Takagi, T. Takamiya, T. Takemura, S. Tomimoto, T. Tsuboi, N. Abe, E. Akaogi, S. Iida, K. Ito, H. Jonouchi, T. Matsushima, H. Miura, M. Miyazaki, S. Okubo, T. Araki, O. Iritani, K. Masuya, S. Morimoto, T. Nakahashi, Y. Wakasa, M. Yanagi, Y. Abe, H. Ito, T. Kawakami, Y. Kawamorita, H. Okamoto, H. Omori, T. Suzuki, T. Yoshida, K. Akiyama, S. Fujita, T. Hamamoto, K. Hasegawa, M. Hattori, H. Imachi, T. Ishida, H. Ishihama, K. Kaifu, H. Kishikawa, M. Kono, M. Kunishige, T. Maeta, H. Masugata, I. Matsumoto, N. Matsuoka, H. Miki, S. Mori, T. Morita, Y. Nishijima, E. Ohashi, Y. Okauchi, T. Okura, Y. Onishi, K. Ono, S. Senda, I. Seo, Y. Sugimoto, M. Tada, K. Yokoi, K. Yoshinare, K. Arikawa, Y. Hayashi, K. Iida, S. Miyata, H. Mizoguchi, A. Osako, S. Saishoji, I. Shimozono, S. Takenouchi, S. Tanaka, T. Furuki, N. Hatori, T. Iwaki, E. Kametsu, T. Kawafune, I. Kobayashi, T. Kubo, I. Michishita, F. Nonaka, H. Numata, A. Ogata, K. Okubo, T. Sano, R. Sawada, T. Sekino, N. Shimizu, H. Shionoiri, H. Tsuchiya, Y. Watanabe, H. Yamamoto, G. Yasuda, M. Aoki, Y. Iwasaki, H. Kawamoto, S. Kitagawa, M. Matsumoto, M. Nishinaga, M. Nishiyama, K. Tsuboi, I. Ueda, T. Yabe, H. Yamada, T. Yoshida, K. Azuma, O. Doi, R. Fukami, Y. Horio, Y. Ichikawa, S. Ikeda, T. Inaba, S. Mimori, K. Ohmori, K. Sasaki, A. Sato, H. Toyama, Y. Toyama, T. Hamasaki, H. Hayashi, T. Isono, S. Kageyama, K. Komaki, S. Matoba, H. Matsubara, T. Matubara, C. Nakagawa, D. Nishi, M. Nishi, K. Oiwa, H. Takamatsu, H. Takashima, T. Takegami, K. Takenaka, H. Yamada, Y. Yasuda, M. Horiguchi, J. Iemura, N. Isaka, T. Ishiga, T. Kato, T. Kitamura, M. Kobayashi, M. Setsuda, K. Shimono, M. Abe, T. Abe, Y. Abe, Y. Akino, H. Ebina, G. Hirasawa, K. Hirasawa, H. Kamada, M. Kishi, K. Kohama, S. Kyogoku, K. Matsuo, Y. Meguro, S. Miyasato, K. Morita, H. Nakagawa, Y. Otake, H. Saito, A. Sasaki, I. Sasaki, S. Sato, N. Uchida, Y. Utsumi, S. Yamaguchi, K. Hosokawa, Y. Ishiyama, S. Kariya, H. Komidori, M. Kuwabara, H. Ohta, S. Sonoda, M. Takii, N. Wake, N. Yokota, A. Iijima, T. Shinozaki, T. Takeda, A. Ito, H. Kawano, Y. Koide, H. Matsuoka, K. Nakao, K. Yamaguchi, A. Yamanaka, Y. Furiya, T. Kimu, Y. Kuga, Y. Nishida, Y. Saito, K. Sugie, T. Takami, M. Yamasaki, Y. Kaneko, H. Kawabata, S. Nakayama, Y. Abe, H. Ando, T. Fujino, K. Gotoh, T. Kakuma, I. Katsuragi, A. Kuroda, T. Masaki, K. Ninomiya, K. Okita, H. Ono, T. Watanabe, A. Yoshiiwa, K. Abe, S. Deguchi, F. Ikeda, H. Kataoka, N. Komai, K. Koten, K. Kusano, N. Maeda, H. Makino, S. Matano, T. Ohe, K. Shikata, M. Gushiken, R. Hamada, K. Matsushima, T. Shimabukuro, S. Tohma, T. Akagi, F. Akai, T. Amatsu, N. Babaya, S. Ban, K. Fujii, M. Fujimoto, Y. Fujimura, S. Fukumoto, M. Funauchi, H. Hanada, K. Hasegawa, N. Hayashi, T. Hibuse, M. Higashida, H. Honde, A. Imagawa, Y. Imamura, S. Inoue, R. Ishii, K. Ishikawa, K. Ishitani, H. Ito, S. Kaito, A. Kamitani, K. Kamiya, N. Kasayuki, R. Kawanami, T. Kawasaki, Y. Kijima, K. Kinoshita, M. Kishibuchi, Y. Kitamura, M. Kobayashi, T. Kono, Y. Maeda, K. Masaki, H. Matsumoto, S. Matsuoka, R. Matsuwaka, K. Minamikata, M. Miyagawa, H. Miyamoto, M. Miyamoto, E. Miyazaki, K. Miyoshi, M. Mune, N. Nakagawa, Y. Nakagawa, F. Nakamura, T. Nakamura, K. Nakanishi, Y. Nakatani, J. Nariyama, H. Nishida, M. Nishino, M. Nishiyama, K. Nishizawa, R. Nohara, A. Nose, H. Ogasawara, R. Ogawa, Y. Ohno, M. Ojima, Y. Okuyama, H. Otani, S. Otani, H. Park, H. Saito, A. Sakai, H. Sakamoto, H. Sata, Y. Sekine, T. Shinozuka, T. Suga, K. Sugimoto, M. Sugiyama, K. Suyama, K. Suyama, J. Tachi, T. Takagi, C. Takaori, M. Takenaka, T. Tamai, K. Tanaka, Y. Tanaka, K. Tane, M. Taniura, N. Tatsuda, Y. Teramoto, K. Teranaka, S. Teranishi, J. Terasaki, K. Toki, K. Tsuji, Y. Tsuji, T. Tsunetoshi, K. Ujino, S. Umeki, N. Wakagi, N. Wakaki, K. Yamaguchi, Y. Yamamoto, S. Yanagitani, M. Yoshida, H. Yoshimoto, H. Yoshioka, H. Ikeda, M. Matsumoto, K. Nagae, M. Nishiyama, K. Noda, M. Ohga, M. Akui, H. Aoki, J. Arafune, M. Arai, T. Arai, I. Asami, K. Eguchi, T. Fujino, H. Fujinuma, H. Fukata, J. Fukuda, T. Hamasaki, M. Haneda, I. Hisauchi, T. Hogi, M. Ichikawa, T. Iijima, H. Inoue, Y. Inoue, T. Kakinuma, H. Kanai, U. Kaneko, T. Kano, T. Katsumi, T. Kawashima, K. Kogure, O. Komuro, Y. Kubouchi, N. Kujirai, K. Kurokawa, T. Lee, K. Maeda, T. Majima, Y. Maruyama, S. Mashiba, K. Mashiko, K. Matsumoto, M. Matsuzawa, Y. Mitsugi, J. Morita, C. Nakajima, Y. Nakazato, Y. Nashida, H. Nasuhara, Y. Numajiri, T. Ogasawara, T. Okudaira, I. Osawa, N. Otani, A. Otsuka, Y. Ozawa, T. Sakai, Y. Sakai, K. Shimizu, T. Shinozaki, M. Shirai, K. Shiroma, H. Shuto, H. Suzuki, A. Tada, M. Takagi, K. Takahashi, N. Takahashi, A. Taniguchi, Y. Tonegawa, M. Toyoda, T. Tsuchiya, M. Uchida, H. Uchino, H. Wada, O. Wada, H. Yoshioka, H. Horie, M. Ichikawa, K. Ikenoue, T. Kawashima, H. Mizuhara, S. Ono, S. Ishikawa, K. Kawakami, S. Yano, N. Kubota, A. Nakagawa, T. Shigemasa, S. Suwa, T. Akabane, M. Amagai, Y. Asanobu, S. Horinaka, T. Iijima, K. Kasai, T. Kataoka, M. Kobayashi, T. Masuda, I. Nakano, M. Namekawa, A. Numabe, A. Ono, K. Sakata, I. Taguchi, T. Tomotsune, S. Toyoda, M. Arizumi, Y. Morimoto, A. Ota, S. Sawada, K. Yata, H. Akita, T. Akitsu, K. Amemiya, M. Ando, N. Aoki, J. Aoyagi, T. Baba, T. Degawa, S. Eto, K. Fujimoto, H. Fukuda, T. Furukawa, I. Goto, A. Hachiya, Y. Hanatani, K. Hara, T. Haruta, K. Hasegawa, T. Hatano, M. Hayashi, T. Hirano, M. Hiratsuka, Y. Horikawa, T. Horiuchi, M. Hosoya, K. Ichikawa, K. Iguchi, H. Imai, K. Ishibashi, K. Ishida, Y. Ishii, S. Ishiwata, T. Iwama, H. Kadota, S. Kaku, Y. Kamisaka, R. Kanbara, T. Kanematsu, A. Kashiwagi, I. Kawa, B. Kawai, M. Kawai, S. Kiuchi, T. Kiyozuka, S. Koba, H. Kobayashi, K. Koike, H. Kojima, E. Koshibu, Y. Koshibu, I. Kubo, K. Kuga, T. Kushiro, S. Miyakata, M. Miyakawa, F. Miyoshi, Y. Mochida, N. Moriyama, T. Myojo, M. Nagashima, H. Nakada, T. Nakai, T. Nakamura, Y. Nakaya, M. Nishizawa, S. Nishizawa, K. Oba, Y. Obu, N. Ohara, M. Okazaki, Y. Okazaki, K. Okumura, T. Ono, Y. Osamura, M. Otsuka, M. Ouchi, N. Sakamoto, Y. Sakata, S. Saneshige, M. Sasajima, T. Satoi, Y. Sengoku, K. Shibuya, H. Shimizu, K. Shimokado, M. Shoji, H. Tabata, A. Takahashi, H. Takakura, T. Takao, M. Taya, H. Tomonari, T. Tsunematsu, A. Uehata, T. Umezawa, H. Usui, T. Watanabe, Y. Yajima, F. Yamada, K. Yamada, A. Yamaguchi, T. Yamaguchi, K. Yamamoto, M. Yamamoto, T. Hamada, I. Hisatome, K. Arita, M. Arita, E. Doi, H. Furuta, T. Hano, T. Hashizume, A. Hibino, N. Kodama, A. Saika, J. Ueda, T. Fujita, T. Ito, M. Sakano, T. Sugawara, H. Tachibana, H. Toda, S. Fujimoto, T. Furui, Y. Hadano, T. Kaneko, A. Kawabata, S. Kawamoto, M. Mezuki, M. Mochizuki, M. Nakatsuka, S. Ono, N. Tahara, M. Kuroda, H. Manabe

    Journal of hypertension   32 ( 10 )   2054 - 2063   2014.10

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    DOI: 10.1097/HJH.0000000000000281

  • Intramyocellular lipid is increased in the skeletal muscle of patients with dilated cardiomyopathy with lowered exercise capacity Reviewed

    Kagami Hirabayashi, Shintaro Kinugawa, Takashi Yokota, Shingo Takada, Arata Fukushima, Tadashi Suga, Masashige Takahashi, Taisuke Ono, Noriteru Morita, Masashi Omokawa, Kuniaki Harada, Noriko Oyama-Manabe, Hiroaki Shirato, Shouji Matsushima, Koichi Okita, Hiroyuki Tsutsui

    International Journal of Cardiology   176 ( 3 )   1110 - 1112   2014.10

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    DOI: 10.1016/j.ijcard.2014.07.113

  • Pioglitazone ameliorates the lowered exercise capacity and impaired mitochondrial function of the skeletal muscle in type 2 diabetic mice Reviewed

    Shingo Takada, Kagami Hirabayashi, Shintaro Kinugawa, Takashi Yokota, Shouji Matsushima, Tadashi Suga, Tomoyasu Kadoguchi, Arata Fukushima, Tsuneaki Homma, Wataru Mizushima, Yoshihiro Masaki, Takaaki Furihata, Ryoichi Katsuyama, Koichi Okita, Hiroyuki Tsutsui

    European Journal of Pharmacology   740   690 - 696   2014.10

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    DOI: 10.1016/j.ejphar.2014.06.008

  • (Pro)renin receptor in skeletal muscle is involved in the development of insulin resistance associated with postinfarct heart failure in mice Reviewed

    Arata Fukushima, Shintaro Kinugawa, Shingo Takada, Shouji Matsushima, Mochamad Ali Sobirin, Taisuke Ono, Masashige Takahashi, Tadashi Suga, Tsuneaki Homma, Yoshihiro Masaki, Takaaki Furihata, Tomoyasu Kadoguchi, Takashi Yokota, Koichi Okita, Hiroyuki Tsutsui

    American Journal of Physiology - Endocrinology and Metabolism   307 ( 6 )   E503 - E514   2014.9

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    DOI: 10.1152/ajpendo.00449.2013

  • Clinical characteristics and CHADS2 score in patients with heart failure and atrial fibrillation Insights from the Japanese Cardiac Registry of Heart Failure in Cardiology (JCARE-CARD) Reviewed

    Sanae Hamaguchi, Shintaro Kinugawa, Shouji Matsushima, Arata Fukushima, Takashi Yokota, Mamoru Sakakibara, Hisashi Yokoshiki, Miyuki Tsuchihashi-Makaya, Hiroyuki Tsutsui

    International Journal of Cardiology   176 ( 1 )   239 - 242   2014.9

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    DOI: 10.1016/j.ijcard.2014.06.068

  • Physiological and pathological functions of NADPH oxidases during myocardial ischemia-reperfusion Reviewed

    Shouji Matsushima, Hiroyuki Tsutsui, Junichi Sadoshima

    Trends in Cardiovascular Medicine   24 ( 5 )   202 - 205   2014.7

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    DOI: 10.1016/j.tcm.2014.03.003

  • Hyponatremia is an independent predictor of adverse clinical outcomes in hospitalized patients due to worsening heart failure Reviewed

    Sanae Hamaguchi, Shintaro Kinugawa, Miyuki Tsuchihashi-Makaya, Shouji Matsushima, Mamoru Sakakibara, Naoki Ishimori, Daisuke Goto, Hiroyuki Tsutsui

    Journal of Cardiology   63 ( 3 )   182 - 188   2014.3

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    DOI: 10.1016/j.jjcc.2013.07.012

  • Elimination of NADPH oxidase activity promotes reductive stress and sensitizes the heart to ischemic injury. Reviewed

    Qiujun Yu, Chi Fung Lee, Wang Wang, Georgios Karamanlidis, Junya Kuroda, Shouji Matsushima, Junichi Sadoshima, Rong Tian

    Journal of the American Heart Association   3 ( 1 )   e000555   2014

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    DOI: 10.1161/JAHA.113.000555

  • Decreased serum brain-derived neurotrophic factor levels are correlated with exercise intolerance in patients with heart failure Reviewed

    Arata Fukushima, Shintaro Kinugawa, Tsuneaki Homma, Yoshihiro Masaki, Takaaki Furihata, Takashi Yokota, Shouji Matsushima, Takahiro Abe, Tadashi Suga, Shingo Takada, Tomoyasu Kadoguchi, Ryoichi Katsuyama, Koji Oba, Koichi Okita, Hiroyuki Tsutsui

    International Journal of Cardiology   168 ( 5 )   e142 - e144   2013.10

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    DOI: 10.1016/j.ijcard.2013.08.073

  • Increased plasma soluble (pro)renin receptor levels are correlated with renal dysfunction in patients with heart failure Reviewed

    Arata Fukushima, Shintaro Kinugawa, Tsuneaki Homma, Yoshihiro Masaki, Takaaki Furihata, Takahiro Abe, Tadashi Suga, Shingo Takada, Tomoyasu Kadoguchi, Koichi Okita, Shouji Matsushima, Hiroyuki Tsutsui

    International Journal of Cardiology   168 ( 4 )   4313 - 4314   2013.10

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    DOI: 10.1016/j.ijcard.2013.04.176

  • Whole body assessment by 18 F-FDG PET in a patient with infective endocarditis Reviewed

    Atsuro Masuda, Osamu Manabe, Masanao Naya, Noriko Oyama-Manabe, Shiro Yamada, Shouji Matsushima, Florian Gaertner, Satoshi Yamada, Hiroyuki Tsutsui, Nagara Tamaki

    Journal of Nuclear Cardiology   20 ( 4 )   641 - 643   2013.8

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    DOI: 10.1007/s12350-013-9722-2

  • Broad suppression of NADPH oxidase activity exacerbates ischemia/reperfusion injury through inadvertent downregulation of hypoxia-inducible factor-1α and upregulation of peroxisome proliferator-activated receptor-α Reviewed

    112 ( 8 )   1135 - 1149   2013.4

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    RATIONALE: NADPH oxidase (Nox) 2 and Nox4 are major components of the Nox family which purposefully produce reactive oxidative species, namely O 2- and H2O2, in the heart. The isoform-specific contribution of Nox2 and Nox4 to ischemia/reperfusion (I/R) injury is poorly understood. OBJECTIVE: We investigated the role of Nox2 and Nox4 in mediating oxidative stress and myocardial injury during I/R using loss-of-function mouse models. METHODS AND RESULTS: Systemic (s) Nox2 knockout (KO), sNox4 KO, and cardiac-specific (c) Nox4 KO mice were subjected to I/R (30 minutes/24 hours, respectively). Both myocardial infarct size/area at risk and O2- production were lower in sNox2 KO, sNox4 KO, and cNox4 KO than in wild-type mice. Unexpectedly, however, the myocardial infarct size/area at risk was greater, despite less O2- production, in sNox2 KO+cNox4 KO (double-KO) mice and transgenic mice (Tg) with cardiac-specific expression of dominant-negative Nox, which suppresses both Nox2 and Nox4, than in wild-type or single KO mice. Hypoxia-inducible factor-1α was downregulated whereas peroxisome proliferator-activated receptor-α was upregulated in Tg-dominant-negative Nox mice. A cross with mice deficient in prolyl hydroxylase 2, which hydroxylates hypoxia-inducible factor-1α, rescued the I/R injury and prevented upregulation of peroxisome proliferator-activated receptor-α in Tg-dominant-negative Nox mice. A cross with peroxisome proliferator-activated receptor-α KO mice also attenuated the injury in Tg- dominant-negative Nox mice. CONCLUSIONS: Both Nox2 and Nox4 contribute to the increase in reactive oxidative species and injury by I/R. However, low levels of reactive oxidative species produced by either Nox2 or Nox4 regulate hypoxia-inducible factor-1α and peroxisome proliferator-activated receptor-α, thereby protecting the heart against I/R, suggesting that Noxs also act as a physiological sensor for myocardial adaptation.

    DOI: 10.1161/CIRCRESAHA.111.300171

  • Interacting with thioredoxin-1-disease or no disease? Reviewed

    Tim Christian Zschauer, Shouji Matsushima, Joachim Altschmied, Dan Shao, Junichi Sadoshima, Judith Haendeler

    Antioxidants and Redox Signaling   18 ( 9 )   1053 - 1062   2013.3

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    DOI: 10.1089/ars.2012.4822

  • Increased oxidative stress in the nucleus caused by Nox4 mediates oxidation of HDAC4 and cardiac hypertrophy Reviewed

    Shouji Matsushima, Junya Kuroda, Tetsuro Ago, Peiyong Zhai, Ji Yeon Park, Lai Hua Xie, Bin Tian, Junichi Sadoshima

    Circulation research   112 ( 4 )   651 - 663   2013.2

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    DOI: 10.1161/CIRCRESAHA.112.279760

  • Oxidative stress and heart failure Reviewed

    Hiroyuki Tsutsui, Shintaro Kinugawa, Shouji Matsushima

    American Journal of Physiology - Heart and Circulatory Physiology   301 ( 6 )   2181 - 2190   2011.12

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    DOI: 10.1152/ajpheart.00554.2011

  • Application of recombinant thioredoxin1 for treatment of heart disease Reviewed

    Shouji Matsushima, Daniela Zablocki, Junichi Sadoshima

    Journal of Molecular and Cellular Cardiology   51 ( 4 )   570 - 573   2011.10

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    DOI: 10.1016/j.yjmcc.2010.09.020

  • Oxidative stress impairs insulin signal in skeletal muscle and causes insulin resistance in postinfarct heart failure Reviewed

    Yukihiro Ohta, Shintaro Kinugawa, Shouji Matsushima, Taisuke Ono, Mochamad A. Sobirin, Naoki Inoue, Takashi Yokota, Kagami Hirabayashi, Hiroyuki Tsutsui

    American Journal of Physiology - Heart and Circulatory Physiology   300 ( 5 )   H1637 - H1644   2011.5

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    DOI: 10.1152/ajpheart.01185.2009

  • Successful termination of recurrent ventricular arrhythmias by adaptive servo-ventilation in a patient with heart failure Reviewed

    Shiro Yamada, Mamoru Sakakibara, Shouji Matsushima, Akimichi Saito, Tsuneaki Homma, Arata Fukushima, Yoshihiro Masaki, Masaya Watanabe, Hirofumi Mitsuyama, Hisashi Yokoshiki, Hiroyuki Tsutsui

    Journal of Cardiology Cases   3 ( 2 )   e57 - e61   2011.4

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    DOI: 10.1016/j.jccase.2011.01.001

  • Regulation of myocardial growth and death by NADPH oxidase Reviewed

    Yasuhiro Maejima, Junya Kuroda, Shouji Matsushima, Tetsuro Ago, Junichi Sadoshima

    Journal of Molecular and Cellular Cardiology   50 ( 3 )   408 - 416   2011.3

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    DOI: 10.1016/j.yjmcc.2010.12.018

  • Oxidative stress in cardiac and skeletal muscle dysfunction associated with diabetes mellitus Reviewed

    Hiroyuki Tsutsui, Shintaro Kinugawa, Shouji Matsushima, Takashi Yokota

    Journal of Clinical Biochemistry and Nutrition   48 ( 1 )   68 - 71   2011.1

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    DOI: 10.3164/jcbn.11-012FR

  • The NADPH oxidase Nox4 and aging in the heart Reviewed

    Tetsuro Ago, Shouji Matsushima, Junya Kuroda, Daniela Zablocki, Takanari Kitazono, Junichi Sadoshima

    Aging   2 ( 12 )   1012 - 1016   2010.12

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    DOI: 10.18632/aging.100261

  • Silent information regulator 1 protects the heart from ischemia/reperfusion Reviewed

    Chiao Po Hsu, Peiyong Zhai, Takanobu Yamamoto, Yasuhiro Maejima, Shouji Matsushima, Nirmala Hariharan, Dan Shao, Hiromitsu Takagi, Shinichi Oka, Junichi Sadoshima

    Circulation   122 ( 21 )   2170 - 2182   2010.11

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    DOI: 10.1161/CIRCULATIONAHA.110.958033

  • Successful adaptive servo-ventilation for patients with acute cardiogenic pulmonary edema due to severe aortic stenosis Reviewed

    Mamoru Sakakibara, Shiro Yamada, Shouji Matsushima, Akimichi Saito, Yoshihiro Masaki, Tsuneaki Honma, Suguru Kubota, Yoshiro Matsui, Hiroyuki Tsutsui

    Journal of Cardiology Cases   2 ( 2 )   e115 - e118   2010.10

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    DOI: 10.1016/j.jccase.2010.05.003

  • NADPH oxidase 4 (Nox4) is a major source of oxidative stress in the failing heart Reviewed

    Junya Kuroda, Tetsuro Ago, Shouji Matsushima, Peiyong Zhai, Michael D. Schneider, Junichi Sadoshima

    Proceedings of the National Academy of Sciences of the United States of America   107 ( 35 )   15565 - 15570   2010.8

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    DOI: 10.1073/pnas.1002178107

  • Oxidative stress in skeletal muscle impairs mitochondrial respiration and limits exercise capacity in type 2 diabetic mice Reviewed

    Takashi Yokota, Shintaro Kinugawa, Kagami Hirabayashi, Shouji Matsushima, Naoki Inoue, Yukihiro Ohta, Sanae Hamaguchi, Mochamad A. Sobirin, Taisuke Ono, Tadashi Suga, Satoshi Kuroda, Shinya Tanaka, Fumio Terasaki, Koichi Okita, Hiroyuki Tsutsui

    American Journal of Physiology - Heart and Circulatory Physiology   297 ( 3 )   H1069 - H1077   2009.9

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    DOI: 10.1152/ajpheart.00267.2009

  • Increased myocardial NAD(P)H oxidase-derived superoxide causes the exacerbation of postinfarct heart failure in type 2 diabetes Reviewed

    Shouji Matsushima, Shintaro Kinugawa, Takashi Yokota, Naoki Inoue, Yukihiro Ohta, Sanae Hamaguchi, Hiroyuki Tsutsui

    American Journal of Physiology - Heart and Circulatory Physiology   297 ( 1 )   H409 - H416   2009.7

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    DOI: 10.1152/ajpheart.01332.2008

  • Left main coronary artery atresia diagnosed by multidetector computed tomography Reviewed

    Takahiko Saito, Masatoshi Motohashi, Shouji Matsushima, Naotaka Saito, Takehiro Kubota, Kimitaka Tasai, Hiroshi Asajima

    International Journal of Cardiology   135 ( 1 )   e27 - e29   2009.6

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    DOI: 10.1016/j.ijcard.2008.03.068

  • Mitochondrial oxidative stress and dysfunction in myocardial remodelling Reviewed

    Hiroyuki Tsutsui, Shintaro Kinugawa, Shouji Matsushima

    Cardiovascular research   81 ( 3 )   449 - 456   2009.2

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    DOI: 10.1093/cvr/cvn280

  • QT prolongation and torsade de pointes associated with solifenacin in an 81-year-old woman Reviewed

    Hiroshi Asajima, Yohei Sekiguchi, Shoji Matsushima, Naotaka Saito, Takahiko Saito

    British journal of clinical pharmacology   66 ( 6 )   896 - 897   2008.12

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    DOI: 10.1111/j.1365-2125.2008.03298.x

  • Oxidative stress and mitochondrial DNA damage in heart failure Reviewed

    Hiroyuki Tsutsui, Shintaro Kinugawa, Shouji Matsushima

    Circulation Journal   72 ( SUPPL. A )   A31 - A37   2008

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    DOI: 10.1253/circj.CJ-08-0014

  • Angiotensin II type 1 receptor blocker attenuates myocardial remodelling and preserves diastolic function in diabetic heart Reviewed

    Hiroyuki Tsutsui, Shouji Matsushima, Shintaro Kinugawa, Tomomi Ide, Naoki Inoue, Yukihiro Ohta, Takashi Yokota, Sanae Hamaguchi, Kenji Sunagawa

    Hypertension Research   30 ( 5 )   439 - 449   2007.5

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    DOI: 10.1291/hypres.30.439

  • Angiotensin II type 1 receptor blocker attenuates exacerbated left ventricular remodeling and failure in diabetes-associated myocardial infarction Reviewed

    Hidenori Matsusaka, Shintaro Kinugawa, Tomomi Ide, Shouji Matsushima, Tetsuya Shiomi, Toru Kubota, Kenji Sunagawa, Hiroyuki Tsutsui

    Journal of Cardiovascular Pharmacology   48 ( 3 )   95 - 102   2006.9

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    DOI: 10.1097/01.fjc.0000245405.41317.60

  • Targeted deletion of p53 prevents cardiac rupture after myocardial infarction in mice Reviewed

    Hidenori Matsusaka, Tomomi Ide, Shouji Matsushima, Masaki Ikeuchi, Toru Kubota, Kenji Sunagawa, Shintaro Kinugawa, Hiroyuki Tsutsui

    Cardiovascular research   70 ( 3 )   457 - 465   2006.6

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    DOI: 10.1016/j.cardiores.2006.02.001

  • Overexpression of mitochondrial peroxiredoxin-3 prevents left ventricular remodeling and failure after myocardial infarction in mice Reviewed

    Shouji Matsushima, Tomomi Ide, Mayumi Yamato, Hidenori Matsusaka, Fumiyuki Hattori, Masaki Ikeuchi, Toru Kubota, Kenji Sunagawa, Yasuhiro Hasegawa, Tatsuya Kurihara, Shinzo Oikawa, Shintaro Kinugawa, Hiroyuki Tsutsui

    Circulation   113 ( 14 )   1779 - 1786   2006.4

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    DOI: 10.1161/CIRCULATIONAHA.105.582239

  • Targeted deletion of matrix metalloproteinase 2 ameliorates myocardial remodeling in mice with chronic pressure overload Reviewed

    Hidenori Matsusaka, Tomomi Ide, Shouji Matsushima, Masaki Ikeuchi, Toru Kubota, Kenji Sunagawa, Shintaro Kinugawa, Hiroyuki Tsutsui

    Hypertension   47 ( 4 )   711 - 717   2006.4

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    DOI: 10.1161/01.HYP.0000208840.30778.00

  • Overexpression of glutathione peroxidase attenuates myocardial remodeling and preserves diastolic function in diabetic heart Reviewed

    Shouji Matsushima, Shintaro Kinugawa, Tomomi Ide, Hidenori Matsusaka, Naoki Inoue, Yukihiro Ohta, Takashi Yokota, Kenji Sunagawa, Hiroyuki Tsutsui

    American Journal of Physiology - Heart and Circulatory Physiology   291 ( 5 )   H2237 - H2245   2006

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    DOI: 10.1152/ajpheart.00427.2006

  • Selective disruption of MMP-2 gene exacerbates myocardial inflammation and dysfunction in mice with cytokine-induced cardiomyopathy Reviewed

    Hidenori Matsusaka, Masaki Ikeuchi, Shouji Matsushima, Tomomi Ide, Toru Kubota, Arthur M. Feldman, Akira Takeshita, Kenji Sunagawa, Hiroyuki Tsutsui

    American Journal of Physiology - Heart and Circulatory Physiology   289 ( 5 58-5 )   H1858 - H1864   2005.11

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    DOI: 10.1152/ajpheart.00216.2005

  • Overexpression of mitochondrial transcription factor A ameliorates mitochondrial deficiencies and cardiac failure after myocardial infarction Reviewed

    Masaki Ikeuchi, Hidenori Matsusaka, Dongchon Kang, Shouji Matsushima, Tomomi Ide, Toru Kubota, Toshiyuki Fujiwara, Naotaka Hamasaki, Akira Takeshita, Kenji Sunagawa, Hiroyuki Tsutsui

    Circulation   112 ( 5 )   683 - 690   2005.8

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    DOI: 10.1161/CIRCULATIONAHA.104.524835

  • Inhibition of TGF-β signaling exacerbates early cardiac dysfunction but prevents late remodeling after infarction Reviewed

    64 ( 3 )   526 - 535   2004.12

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    Transforming growth factor (TGF)-β promotes the deposition of extracellular matrix protein and also acts as an anti-inflammatory cytokine. These biological effects might be involved in the development and progression of left ventricular (LV) remodeling and failure after myocardial infarction (MI). However, its pathophysiological significance remains obscure in post-MI hearts. Anterior MI was produced in mice by ligating the left coronary artery. TGF-β mRNA levels increased in both infarcted and noninfarcted LV after MI. To block TGF-β signaling during the early phase of MI, an extracellular domain of TGF-β type II receptor (TβIIR) plasmid was transfected into the limb skeletal muscles 7 days before ligation. TβIIR increased the mortality during 24 h of MI, as well as exacerbated LV dilatation and contractile dysfunction, the infiltration of neutrophils, and gene expression of tumor necrosis factor-α, interleukin-1β, and monocyte chemoattractant protein-1 compared with nontreated MI mice despite the comparable infarct size. Next, to block TGF-β signaling during the later phase, TβIIR was transfected into mice at days 0 and 7 after ligation. At 4 weeks, LV dilatation and contractile dysfunction in association with myocyte hypertrophy and interstitial fibrosis of noninfarcted LV seen in MI mice were prevented by TβIIR. The activation of TGF-β is protective against ischemic myocardial damage during the early phase. However, the beneficial effects might be lost, when its expression is sustained, thereby leading to LV remodeling and failure after MI.

    DOI: 10.1016/j.cardiores.2004.07.017

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Books

  • 「心不全の概念を理解しよう」:実践!心不全療養指導士

    松島将士( Role: Joint author)

    2023.3 

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    Language:Japanese  

  • 心不全の疫学と病型

    松島 将士、筒井裕之

    臨床循環器学 (文光堂)  2021.6 

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    Responsible for pages:35号(Vol.11 No.1) 50-54ページ, 2021年   Language:Japanese   Book type:General book, introductory book for general audience

  • 糖尿病における心筋障害のメカニズム

    松島 将士( Role: Sole author)

    医歯薬出版  2020.7 

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    Language:Japanese   Book type:General book, introductory book for general audience

  • 実験医学別冊 もっとよくわかる!循環器学と精密医療

    松島将士( Role: Joint author)

    羊土社  2020.7 

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    Language:Japanese   Book type:Scholarly book

  • 実験医学別冊 もっとよくわかる!循環器学と精密医療

    松島将士( Role: Joint author)

    羊土社  2020.7 

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    Language:English   Book type:Scholarly book

Presentations

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MISC

  • 「β遮断薬・α遮断薬」

    松島 将士

    2016.6

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    Language:Japanese   Publishing type:Article, review, commentary, editorial, etc. (scientific journal)  

  • 治療法の再整理とアップデートのために 専門家による私の治療 慢性心不全

    松島 将士, 筒井 裕之

    日本医事新報   ( 5117 )   46 - 47   2022.5   ISSN:0385-9215

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    Language:Japanese   Publisher:(株)日本医事新報社  

  • ミトコンドリア機能障害・ERストレス Reviewed

    松島 将士

    2021.6

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    Language:Japanese   Publishing type:Article, review, commentary, editorial, etc. (scientific journal)  

  • 難治性疾患(難病)を学ぶ 肥大型心筋症 Reviewed

    松島将士、筒井裕之

    遺伝子医学 (メディカルドウ)   2020.7

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    Language:Japanese   Publishing type:Article, review, commentary, editorial, etc. (scientific journal)  

  • 診断基準と疫学を識る-拡張型心筋症のすべて

    松島 将士、筒井裕之

    2019.8

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    Language:Japanese   Publishing type:Article, review, commentary, editorial, etc. (scientific journal)  

  • MRAの多施設共同研究を解説する-EMPHASIS-HFとJ-EMPHASIS-HF

    松島 将士

    2019.6

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    Language:Japanese   Publishing type:Article, review, commentary, editorial, etc. (scientific journal)  

  • 拡張相肥大型心筋症

    松島 将士

    2019.6

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    Language:Japanese   Publishing type:Article, review, commentary, editorial, etc. (scientific journal)  

  • 酸化ストレス

    松島 将士

    2019.6

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    Language:Japanese   Publishing type:Article, review, commentary, editorial, etc. (scientific journal)  

  • ミトコンドリア機能異常による心不全

    松島 将士

    2019.6

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    Language:Japanese   Publishing type:Article, review, commentary, editorial, etc. (scientific journal)  

  • NADPH oxidase

    2018.6

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    Language:Japanese   Publishing type:Article, review, commentary, editorial, etc. (scientific journal)  

  • Helicobacter pyloriと非胃・十二指腸疾患とのかかわりはここまで明らかになった

    松島 将士、松島 瑠美子

    2017.12

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    Language:Japanese   Publishing type:Article, review, commentary, editorial, etc. (scientific journal)  

  • 心筋リモデリングにおけるFynによるNox4制御機構

    松島 将士、 佐渡島純一、筒井裕之

    循環器専門医   2017.9

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    Language:Japanese   Publishing type:Article, review, commentary, editorial, etc. (scientific journal)  

  • 心筋リモデリングと酸化ストレス

    松島 将士

    月刊心臓   2017.8

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    Language:Japanese   Publishing type:Article, review, commentary, editorial, etc. (scientific journal)  

  • 高血圧患者のECG

    松島 将士、筒井裕之

    血圧   2017.6

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    Language:Japanese   Publishing type:Article, review, commentary, editorial, etc. (scientific journal)  

  • 心不全の疫学的特徴と臨床像

    松島 将士、筒井裕之

    2017.4

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    Language:Japanese   Publishing type:Article, review, commentary, editorial, etc. (scientific journal)  

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Professional Memberships

  • 日本循環器学会、日本心不全学会、日本心臓病学会、日本心臓リハビリテーション学会

  • 日本循環器学会、日本心不全学会、日本心臓病学会、日本心臓リハビリテーション学会

  • 日本循環器学会、日本心不全学会、日本心臓病学会、日本心臓リハビリテーション学会、日本内科学会

  • 日本循環器学会、日本心不全学会、日本心臓病学会、日本心臓リハビリテーション学会、日本内科学会、アメリカ心臓協会

  • 日本循環器学会、日本心不全学会、日本心臓病学会、日本心臓リハビリテーション学会、日本内科学会、アメリカ心臓協会

Committee Memberships

  • Councilor   Domestic

    2024.4 - 2026.3   

  • 日本循環器学会   九州支部評議員   Domestic

    2024.4 - 2026.3   

  • Organizer   Foreign country

    2022.6 - 2022.1   

  • Councilor   Foreign country

    2020.4 - 2024.3   

  • 日本心不全学会   学術委員   Domestic

    2016.11 - 2023.10   

Academic Activities

  • Screening of academic papers

    Role(s): Peer review

    2023

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    Type:Peer review 

    Number of peer-reviewed articles in foreign language journals:16

  • Screening of academic papers

    Role(s): Peer review

    2022

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    Type:Peer review 

    Number of peer-reviewed articles in foreign language journals:5

  • Screening of academic papers

    Role(s): Peer review

    2021

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    Type:Peer review 

    Number of peer-reviewed articles in foreign language journals:10

  • Screening of academic papers

    Role(s): Peer review

    2020

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    Type:Peer review 

    Number of peer-reviewed articles in foreign language journals:15

  • Screening of academic papers

    Role(s): Peer review

    2019

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    Type:Peer review 

    Number of peer-reviewed articles in foreign language journals:12

  • 事務局 International contribution

    ISHR日本部会  ( 東京 ) 2018.12

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    Type:Competition, symposium, etc. 

  • Screening of academic papers

    Role(s): Peer review

    2018

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    Type:Peer review 

    Number of peer-reviewed articles in foreign language journals:10

  • 座長(Chairmanship)

    第20回日本心不全学会  ( 札幌 ) 2016.10

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    Type:Competition, symposium, etc. 

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Research Projects

  • 心不全における細胞質内ミトコンドリアDNA蓄積と炎症惹起の新規分子機序の解明

    2024.4 - 2027.3

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    Authorship:Principal investigator 

  • 心不全における細胞質内ミトコンドリアDNA蓄積と炎症惹起の新規分子機序の解明

    Grant number:24K11218  2024 - 2026

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    松島 将士, 瀬戸山 大樹, 絹川 真太郎

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    Authorship:Principal investigator  Grant type:Scientific research funding

    本研究は、心筋リモデリング・心不全の病態形成・進展における細胞質内ミトコンドリアDNA蓄積の機序を明らかにするとともに、その制御による心筋炎症抑制という独自のパラダイムに基づく新たな心筋リモデリング・心不全の予防・治療法の開発を目指すものである。 具体的には以下の点を明らかにすることを目的とする。
    1)心不全に陥った心筋において細胞質内ミトコンドリアDNA蓄積はどのように制御されているのか?
    2)細胞質内ミトコンドリアDNAによる炎症シグナルはどのように活性化されるのか?
    3)新規細胞質内ミトコンドリアDNA制御因子への介入で心筋炎症、心不全は改善するか?

    CiNii Research

  • Novel Mechanisms of Inflammation in Pulmonary Hypertension

    Grant number:23K07579  2023.4 - 2026.3

    Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

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    Grant type:Scientific research funding

    CiNii Research

  • 心不全患者における腎性貧血の臨床的意義の解明に関する研究

    2023 - 2027

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    Grant type:Contract research

  • O結合グリコシル化制御に基づくサルコペニアの新規治療法開発

    Grant number:22K19754  2022.6 - 2024.3

    科学研究費助成事業  挑戦的研究(萌芽)

    絹川 真太郎, 松島 将士

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    Grant type:Scientific research funding

    本研究は、『加齢における骨格筋萎縮の進展にタンパク合成や分解に関わる種々のタンパクのO-GLcNAc化修飾が重要な役割を果たしている』という仮説を立て、O-GlcNAc化の制御による骨格筋萎縮の予防・治療法を開発することを目的とする。骨格筋が生体の代謝の中心であることに注目し、その代謝産物による翻訳後修飾であり、リン酸化と競合的に働くO-GlcNAc化修飾に着目した点が、本研究の新規性である。本研究では、これまで注目されていなかったO-GlcNAc化修飾に注目して、加齢における骨格筋萎縮にO-GlcNAc化修飾が重要な役割を果たしているのではないか、という学術的に根本的な疑問の解決に挑戦する。

    CiNii Research

  • 心不全におけるミトコンドリア-小胞体接触の役割の解明と新規治療の開発

    2022.4 - 2025.3

  • Pathophysiology and Clinical Impact of Anemia in Patients with Advanced Heart Failure

    Grant number:22K08103  2022.4 - 2025.3

    Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

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    Grant type:Scientific research funding

    CiNii Research

  • Golgi apparatus-centered organelle network in cardiac remodeling

    Grant number:23K24331  2022.4 - 2025.3

    Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

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    Grant type:Scientific research funding

    CiNii Research

  • Pathobiological role of Ca2+/calmodulin-dependent PDE1 in HFpEF

    Grant number:22K08126  2022.4 - 2025.3

    Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

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    Grant type:Scientific research funding

    CiNii Research

  • Establishment of novel therapy for heart failure via mitochondria quality control by Mieap in cardiomyocytes

    Grant number:21K19485  2021.7 - 2023.3

    Grants-in-Aid for Scientific Research  Grant-in-Aid for Challenging Research (Exploratory)

    Tsutsui Hiroyuki

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    Grant type:Scientific research funding

    Impairment of cardiac function was accompanied by an increase in the protein level of Mieap in post-infarct failing myocardium. Mieap was co-stained with mitochondria in cultured cardiomyocytes by immunostaining, suggesting that Mieap is localized in mitochondria. Furthermore, knockout of Mieap increased hydrogen peroxide-induced cell death in cultured cardiomyocytes. Mieap knockout mice had increased mortality after myocardial infarction compared to wild-type mice. In addition, cardiomegaly progressed, cardiac hypertrophy progressed, cardiac function deterioration was accelerated, and lung weight and heart weight increased. These findings indicated that Mieap, as a mitochondrial protein, has cardioprotective action against oxidative stress, which promotes the progress of myocardial remodeling.

    CiNii Research

  • マイオカインによる老化進展制御機構の解明

    Grant number:21H03360  2021.4 - 2024.3

    科学研究費助成事業  基盤研究(B)

    絹川 真太郎, 佐邊 壽孝, 高田 真吾, 松島 将士, 横田 卓

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    Grant type:Scientific research funding

    健康長寿達成のためには、老化に伴うサルコペニア・フレイルを含む種々の臓器障害の分子基盤の解明および予防法の確立が必要である。近年、骨格筋から分泌されるマイオカインが注目されているが、老化進展におけるマイオカインの産生・分泌の全体像は明らかにされていない。本研究では、加齢性のマイオカイン異常が老化進展の要因であるという仮説を検証する。網羅的に経時的な加齢マイオカインプロファイリングを行い、動的バイオマーカー理論に基づく解析により、不可逆的老化への臨界特異点を明らかにする。個々のマイオカイン機能解析を行い、マイオカインをターゲットとしたこれまでに新たなパラダイムに基づく老化遅延策の構築を目指す。

    CiNii Research

  • 心不全の発症・重症化の高精度予測とそれに基づく最適な治療戦略の開発

    2021.4 - 2022.3

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    Authorship:Coinvestigator(s) 

  • 心不全におけるミトコンドリア-小胞体接触の役割の解明と新規治療の開発

    Grant number:21K08082  2021 - 2023

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    松島 将士, 筒井 裕之

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    Authorship:Principal investigator  Grant type:Scientific research funding

    ミトコンドリアと小胞体が直接情報や物質を伝達する接着領域Mitochondria-associated ER membrane(MAM)は動的オルガネラネットワークとして細胞機能の維持に重要な役割をはたしており、疾病の発症基盤として注目されている。ミトコンドリア機能異常と小胞体ストレスを病態基盤として発症する心不全においてこれらのオルガネラ機能に密接に関与するMAMの制御機構の破綻が重要な役割を果たしている可能性がある。本研究の目的は、『心不全におけるMAM形成の意義および分子基盤』を明らかにするとともに、『MAM制御という新たなパラダイムに基づく心不全治療法の開発』を目指すものである。

    CiNii Research

  • 心不全の発症・重症化の高精度予測とそれに基づく最適な治療戦略の開発

    2019.4 - 2019.3

    九州大学 

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    Authorship:Coinvestigator(s) 

  • 心筋リモデリングにおけるスルフィレドキシンによるミトコンドリアレドックス制御機構

    Grant number:19H03655  2019 - 2021

    日本学術振興会  科学研究費助成事業  基盤研究(B)

    筒井 裕之, 康 東天, 松島 将士, 井手 友美, 西村 明幸

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    Authorship:Coinvestigator(s)  Grant type:Scientific research funding

    心不全の病態基盤である心筋リモデリングの形成・進展には心筋細胞のミトコンドリアの酸化ストレスが密接に関与している。スルフィレドキシン(SRX)は、不活性型ペルオキシレドキシン(Prx)を還元し蛋白グルタチオン化を制御する酵素であり、心筋細胞のミトコンドリアレドックス制御の基盤分子と考えられる。本研究は心筋リモデリングにおけるSRXのミトコンドリアレッドクス制御の意義を解明し、SRX機能安定化によるレドックス適正化を介したミトコンドリア機能の保持という独自のパラダイムに基づく新たな心不全の予防・治療法の開発を目指すものである。

    CiNii Research

  • 拡張型心筋症におけるSPARMAの役割

    2019 - 2020

    第6回日本心臓財団・拡張型心筋症治療開発研究助成

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    Authorship:Principal investigator  Grant type:Contract research

  • 心不全の発症・重症化の高精度予測とそれに基づく最適な治療戦略の開発

    2018.4 - 2019.3

    九州大学 

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    Authorship:Coinvestigator(s) 

  • 心不全におけるMAM形成の意義

    2018

    持田記念研究助成

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    Authorship:Principal investigator  Grant type:Contract research

  • 心不全の発症・重症化の高精度予測とそれに基づく最適な治療戦略の開発

    2017.4 - 2019.3

    九州大学 

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    わが国における心不全の発症・重症化の高精度予測とそれに基づく最適な治療戦略の開発を目指す

  • ミトコンドリア蛋白輸送機構の心筋リモデリングにおける意義の解明と治療への応用

    Grant number:17K09581  2017 - 2019

    日本学術振興会  科学研究費助成事業  基盤研究(C)

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    Authorship:Principal investigator  Grant type:Scientific research funding

  • ミトコンドリア蛋白輸送機構の心筋リモデリングにおける意義の解明と治療への応用

    Grant number:17K09581  2017 - 2019

    日本学術振興会  科学研究費助成事業  基盤研究(C)

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    Authorship:Principal investigator  Grant type:Scientific research funding

  • 心筋細胞におけるオルガネラネットワーク制御を介した新たな心不全治療

    2017

    平成29年度持田記念研究助成

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    Authorship:Principal investigator  Grant type:Contract research

  • 心筋リモデリングにおけるミトコンドリア・小胞体間輸送機構の解明と新たな心不全治療

    2017

    平成29年度臨床研究助成奨励賞

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    Authorship:Principal investigator  Grant type:Contract research

  • FynによるNox4の新たな制御機構の解明に関する研究

    2016

    第11回Vascular Biology Innovation Conference研究助成

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    Authorship:Principal investigator  Grant type:Contract research

  • わが国における拡張相肥大型心筋症を対象とした登録観察研究

    2015.4 - 2018.3

    九州大学大学院医学研究院循環器内科学 

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    Authorship:Coinvestigator(s) 

  • 心筋リモデリングにおけるmitoNEETによるミトコンドリア機能制御機構の解明

    Grant number:15H04815  2015 - 2017

    日本学術振興会  科学研究費助成事業  基盤研究(B)

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    Authorship:Coinvestigator(s)  Grant type:Scientific research funding

  • 心血管病における心臓周囲脂肪ミトコンドリアの役割

    Grant number:15K09115  2015 - 2017

    日本学術振興会  科学研究費助成事業  基盤研究(C)

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    Authorship:Coinvestigator(s)  Grant type:Scientific research funding

  • Nox4を介したミトコンドリア形態制御の分子基盤解明による新たな心不全治療の開発

    Grant number:15K19358  2015 - 2016

    科学研究費助成事業  若手研究(B)

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    Authorship:Principal investigator  Grant type:Scientific research funding

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Class subject

  • 学年系統医学Ⅱ(循環器)「病歴・身体診察の基本と胸部X線」

    2023.10 - 2024.3   Second semester

  • 3学年系統医学Ⅱ(循環器)「病歴・身体診察の基本と胸部X線」

    2022.10 - 2023.3   Second semester

  • 臨床医学基本実習「⑧胸部診察(循環器)」

    2022.4 - 2022.9   First semester

  • 臨床医学基本実習「胸部診察②(循環器)」

    2021.10 - 2022.3   Second semester

  • 検査実習 心電図演習

    2020.10 - 2021.3   Second semester

  • 臨床医学基本実習「胸部診察②(循環器)」

    2020.10 - 2021.3   Second semester

  • 臨床医学基本実習(患者実習)

    2020.10 - 2021.3   Second semester

  • 検査実習 心電図演習

    2019.10 - 2020.3   Second semester

  • 臨床医学基本実習(患者実習)

    2019.10 - 2020.3   Second semester

  • 臨床医学基本実習「胸部診察②(循環器)」

    2019.10 - 2020.3   Second semester

  • 検査実習 心電図演習

    2018.10 - 2019.3   Second semester

  • 臨床医学基本実習(患者実習)

    2018.10 - 2019.3   Second semester

  • 臨床医学基本実習「胸部診察②(循環器)」

    2018.10 - 2019.3   Second semester

  • 臨床医学基本実習(患者実習)

    2017.10 - 2018.3   Second semester

  • 検査実習 心電図演習

    2017.10 - 2018.3   Second semester

  • 臨床医学基本実習「胸部診察②(循環器)」

    2017.10 - 2018.3   Second semester

  • 検査実習 心電図演習

    2016.10 - 2017.3   Second semester

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Other educational activity and Special note

  • 2023  Special Affairs 

  • 2022  Special Affairs 

  • 2021  Special Affairs 

  • 2019  Special Affairs 

  • 2018  Special Affairs 

  • 2016  Special Affairs 

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Outline of Social Contribution and International Cooperation activities

  • 米国ニュージャージ医科大学の佐渡島純一教授と共同で心不全の病態解明に関する基礎研究を推進している。

Travel Abroad

  • 2010.3 - 2012.12

    Staying countory name 1:United States   Staying institution name 1:ニュージャージー医科歯科大学

Specialized clinical area

  • Biology / Medicine, Dentistry and Pharmacy / Internal Medicine / Cardiology

Clinician qualification

  • Specialist

    The Japanese Circulation Society(JCS)

Year of medical license acquisition

  • 2001

Notable Clinical Activities

  • 心不全臨床グループの指導医として、重症心不全患者の診療に従事し、人工心臓、心臓移植医療を推進している。