Kyushu University [Tetsuya Matoba (Lecturer) Kyushu University Hospital, Angiocardiology]

Keyword Search

Researcher information

Tetsuya Matoba
Lecturer
Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences
Angiocardiology
Kyushu University Hospital
Last modified date：2023.12.06

Graduate School

Department of Medicine and Surgery
Graduate School of Medical Sciences

Undergraduate School

Department of Clinical Pharmacy
School of Pharmaceutical Sciences

Department of Medicine
School of Medicine

Administration Post

Other

E-Mail

Homepage

Phone

Fax

Academic Degree

Country of degree conferring institution (Overseas)

Field of Specialization

ORCID(Open Researcher and Contributor ID)

Total Priod of education and research career in the foreign country

Outline Activities

Research

Educational

Social

Unauthorized reprint of the contents of this database is prohibited.

1.	Tetsuya Matoba, Kazuo Sakamoto, Michikazu Nakai, Kenzo Ichimura, Masahiro Mohri, Yasuyuki Tsujita, Masao Yamasaki, Yasushi Ueki, Nobuhiro Tanaka, Yohei Hokama, Motoki Fukutomi, Katsutaka Hashiba, Rei Fukuhara, Satoru Suwa, Hirohide Matsuura, Hayato Hosoda, Takahiro Nakashima, Yoshio Tahara, Yoko Sumita, Kunihiro Nishimura, Yoshihiro Miyamoto, Naohiro Yonemoto, Tsukasa Yagi, Eizo Tachibana, Ken Nagao, Takanori Ikeda, Naoki Sato, Hiroyuki Tsutsui, Institutional Characteristics and Prognosis of Acute Myocardial Infarction With Cardiogenic Shock in Japan - Analysis From the JROAD/JROAD-DPC Database., Circulation journal : official journal of the Japanese Circulation Society, 10.1253/circj.CJ-20-0655, 85, 10, 1797-1805, 2021.03, BACKGROUND: The high mortality of acute myocardial infarction (AMI) with cardiogenic shock (i.e., Killip class IV AMI) remains a challenge in emergency cardiovascular care. This study aimed to examine institutional factors, including the number of JCS board-certified members, that are independently associated with the prognosis of Killip class IV AMI patients.Methods and Results:In the Japanese registry of all cardiac and vascular diseases-diagnosis procedure combination (JROAD-DPC) database (years 2012-2016), the 30-day mortality of Killip class IV AMI patients (n=21,823) was 42.3%. Multivariate analysis identified age, female sex, admission by ambulance, deep coma, and cardiac arrest as patient factors that were independently associated with higher 30-day mortality, and the numbers of JCS board-certified members and of intra-aortic balloon pumping (IABP) cases per year as institutional factors that were independently associated with lower mortality in Killip class IV patients, although IABP was associated with higher mortality in Killip classes I-III patients. Among hospitals with the highest quartile (≥9 JCS board-certified members), the 30-day mortality of Killip class IV patients was 37.4%. CONCLUSIONS: A higher numbers of JCS board-certified members was associated with better survival of Killip class IV AMI patients. This finding may provide a clue to optimizing local emergency medical services for better management of AMI patients in Japan..
2.	Satoshi Yasuda, Koichi Kaikita, Masaharu Akao, Junya Ako, Tetsuya Matoba, Masato Nakamura, Katsumi Miyauchi, Nobuhisa Hagiwara, Kazuo Kimura, Atsushi Hirayama, Kunihiko Matsui, Hisao Ogawa, Antithrombotic Therapy for Atrial Fibrillation with Stable Coronary Disease., The New England journal of medicine, 10.1056/NEJMoa1904143, 381, 12, 1103-1113, 2019.09, BACKGROUND: There are limited data from randomized trials evaluating the use of antithrombotic therapy in patients with atrial fibrillation and stable coronary artery disease. METHODS: In a multicenter, open-label trial conducted in Japan, we randomly assigned 2236 patients with atrial fibrillation who had undergone percutaneous coronary intervention (PCI) or coronary-artery bypass grafting (CABG) more than 1 year earlier or who had angiographically confirmed coronary artery disease not requiring revascularization to receive monotherapy with rivaroxaban (a non-vitamin K antagonist oral anticoagulant) or combination therapy with rivaroxaban plus a single antiplatelet agent. The primary efficacy end point was a composite of stroke, systemic embolism, myocardial infarction, unstable angina requiring revascularization, or death from any cause; this end point was analyzed for noninferiority with a noninferiority margin of 1.46. The primary safety end point was major bleeding, according to the criteria of the International Society on Thrombosis and Hemostasis; this end point was analyzed for superiority. RESULTS: The trial was stopped early because of increased mortality in the combination-therapy group. Rivaroxaban monotherapy was noninferior to combination therapy for the primary efficacy end point, with event rates of 4.14% and 5.75% per patient-year, respectively (hazard ratio, 0.72; 95% confidence interval [CI], 0.55 to 0.95; P
3.	Masaki Fujiwara, Tetsuya Matoba, Jun-Ichiro Koga, Arihide Okahara, Daiki Funamoto, Kaku Nakano, Hiroyuki Tsutsui, Kensuke Egashira, Nanoparticle incorporating Toll-like receptor 4 inhibitor attenuates myocardial ischaemia-reperfusion injury by inhibiting monocyte-mediated inflammation in mice., Cardiovascular research, 10.1093/cvr/cvz066, 115, 7, 1244-1255, 2019.06, AIMS: Myocardial ischaemia-reperfusion (IR) injury hampers the therapeutic effect of revascularization in patients with acute myocardial infarction (AMI). Innate immunity for damage-associated protein patterns promotes the process of IR injury; however, the blockade of Toll-like receptor 4 (TLR4) in myocardial IR injury has not been translated into clinical practice. Therefore, we aimed to examine whether the nanoparticle-mediated administration of TAK-242, a chemical inhibitor of TLR4, attenuates myocardial IR injury in a clinically feasible protocol in a mouse model. METHODS AND RESULTS: We have prepared poly-(lactic-co-glycolic acid) nanoparticles containing TAK-242 (TAK-242-NP). TAK-242-NP significantly enhanced the drug delivery to monocytes/macrophages in the spleen, blood, and the heart in mice. Intravenous administration of TAK-242-NP (containing 1.0 or 3.0 mg/kg TAK-242) at the time of reperfusion decreased the infarct size, but the TAK-242 solution did not even when administered at a dosage of 10.0 mg/kg. TAK-242-NP inhibited the recruitment of Ly-6Chigh monocytes to the heart, which was accompanied by decreased circulating HMGB1, and NF-κB activation and cytokine expressions in the heart. TAK-242-NP did not decrease the infarct size further in TLR4-deficient mice, confirming the TLR4-specific mechanism in the effects of TAK-242-NP. Furthermore, TAK-242-NP did not decrease the infarct size further in CCR2-deficient mice, suggesting that monocyte/macrophage-mediated inflammation is the primary therapeutic target of TAK-242-NP. CONCLUSION: The nanoparticle-mediated delivery of TAK-242-NP represent a novel and clinical feasible strategy in patients undergone coronary revascularization for AMI by regulating TLR4-dependent monocytes/macrophages-mediated inflammation..
4.	Tetsuya Matoba, Takahide Kohro, Hideo Fujita, Masaharu Nakayama, Arihiro Kiyosue, Yoshihiro Miyamoto, Kunihiro Nishimura, Hideki Hashimoto, Yasuaki Antoku, Naoki Nakashima, Kazuhiko Ohe, Hisao Ogawa, Hiroyuki Tsutsui, Ryozo Nagai, Architecture of the Japan Ischemic Heart Disease Multimodal Prospective Data Acquisition for Precision Treatment (J-IMPACT) System., International heart journal, 10.1536/ihj.18-113, 60, 2, 264-270, 2019.03, The utilization of electronic medical records and multimodal medical data is an ideal approach to build a real-time and precision registry type study with a smaller effort and cost, which may fill a gap between evidence-based medicine and the real-world clinical practice. The Japan Ischemic heart disease Multimodal Prospective data Acquisition for preCision Treatment (J-IMPACT) project aimed to build an clinical data registry system that electronically collects not only medical records, but also multimodal data, including coronary angiography and percutaneous coronary intervention (PCI) report, in standardized data formats for clinical studies.The J-IMPACT system comprises the standardized structured medical information exchange (SS-MIX), coronary angiography and intervention reporting system (CAIRS), and multi-purpose clinical data repository system (MCDRS) interconnected within the institutional network. In order to prove the concept, we acquired multimodal medical data of 6 consecutive cases that underwent PCI through the J-IMPACT system in a single center. Data items regarding patient background, laboratory data, prescriptions, and PCI/cardiac catheterization report were correctly acquired through the J-IMPACT system, and the accuracy of the multimodal data of the 4 categories was 100% in all 6 cases.The application of J-IMPACT system to clinical studies not only fills the gaps between randomized clinical trials and real-world medicine, but may also provide real-time big data that reinforces precision treatment for each patient..
5.	Masaki Tokutome, Tetsuya Matoba, Yasuhiro Nakano, Arihide Okahara, Masaki Fujiwara, Jun-Ichiro Koga, Kaku Nakano, Hiroyuki Tsutsui, Kensuke Egashira, Peroxisome proliferator-activated receptor-gamma targeting nanomedicine promotes cardiac healing after acute myocardial infarction by skewing monocyte/macrophage polarization in preclinical animal models., Cardiovascular research, 10.1093/cvr/cvy200, 115, 2, 419-431, 2019.02, Aims: Monocyte-mediated inflammation is a major mechanism underlying myocardial ischaemia-reperfusion (IR) injury and the healing process after acute myocardial infarction (AMI). However, no definitive anti-inflammatory therapies have been developed for clinical use. Pioglitazone, a peroxisome proliferator-activated receptor-gamma (PPARγ) agonist, has unique anti-inflammatory effects on monocytes/macrophages. Here, we tested the hypothesis that nanoparticle (NP)-mediated targeting of pioglitazone to monocytes/macrophages ameliorates IR injury and cardiac remodelling in preclinical animal models. Methods and results: We formulated poly (lactic acid/glycolic acid) NPs containing pioglitazone (pioglitazone-NPs). In a mouse IR model, these NPs were delivered predominantly to circulating monocytes and macrophages in the IR heart. Intravenous treatment with pioglitazone-NPs at the time of reperfusion attenuated IR injury. This effect was abrogated by pre-treatment with the PPARγ antagonist GW9662. In contrast, treatment with a pioglitazone solution had no therapeutic effects on IR injury. Pioglitazone-NPs inhibited Ly6Chigh inflammatory monocyte recruitment as well as inflammatory gene expression in the IR hearts. In a mouse myocardial infarction model, intravenous treatment with pioglitazone-NPs for three consecutive days, starting 6 h after left anterior descending artery ligation, attenuated cardiac remodelling by reducing macrophage recruitment and polarizing macrophages towards the pro-healing M2 phenotype. Furthermore, pioglitazone-NPs significantly decreased mortality after MI. Finally, in a conscious porcine model of myocardial IR, pioglitazone-NPs induced cardioprotection from reperfused infarction, thus providing pre-clinical proof of concept. Conclusion: NP-mediated targeting of pioglitazone to inflammatory monocytes protected the heart from IR injury and cardiac remodelling by antagonizing monocyte/macrophage-mediated acute inflammation and promoting cardiac healing after AMI..
6.	Katsuya Honda, Tetsuya Matoba, Yoshibumi Antoku, Jun-Ichiro Koga, Ikuyo Ichi, Kaku Nakano, Hiroyuki Tsutsui, Kensuke Egashira, Lipid-Lowering Therapy With Ezetimibe Decreases Spontaneous Atherothrombotic Occlusions in a Rabbit Model of Plaque Erosion: A Role of Serum Oxysterols., Arteriosclerosis, thrombosis, and vascular biology, 10.1161/ATVBAHA.117.310244, 38, 4, 757-771, 2018.04, [URL], OBJECTIVE: Plaque erosion is increasing its importance as one of the mechanisms of acute coronary syndromes in this statin era. However, the clinical efficacy of currently used lipid-lowering agents in the prevention of thrombotic complications associated with plaque erosion has not been clarified. Therefore, we examined the therapeutic effects of ezetimibe or rosuvastatin monotherapy on spontaneous atherothrombotic occlusion. APPROACH AND RESULTS: Femoral arteries of Japanese white rabbits, fed a high-cholesterol diet, were injured by balloon catheter, and then angiotensin II was continuously administrated. In 94% of these arteries, spontaneous thrombotic occlusions were observed after 5 weeks (median) of balloon injury. Histochemical analyses indicated that the injured arteries had similar pathological features to human plaque erosions; (1) spontaneous thrombotic occlusion, (2) lack of endothelial cells, and (3) tissue factor expression in vascular smooth muscle cells. Ezetimibe (1.0 mg/kg per day), but not rosuvastatin (0.6 mg/kg per day), significantly decreased thrombotic occlusion of arteries accompanied with accelerated re-endothelialization and the decreases of serum oxysterols despite the comparable on-treatment serum cholesterol levels. The 7-ketocholesterol inhibited the migration of human umbilical vein endothelial cells. Both 7-ketocholesterol and 27-hydroxycholesterol increased tissue factor expression in cultured rat vascular smooth muscle cells. Tissue factor expression was also induced by serum from vehicle- or rosuvastatin-treated rabbits, but the induction was attenuated with serum from ezetimibe-treated rabbits. CONCLUSIONS: We have established a novel rabbit model of spontaneous atherothromobotic occlusion without plaque rupture that is feasible to test the therapeutic effects of various pharmacotherapies. Ezetimibe may decrease atherothrombotic complications after superficial plaque erosion by reducing serum oxysterols..
7.	Susumu Takase, Tetsuya Matoba, Soichi Nakashiro, Yasushi Mukai, Shujiro Inoue, Keiji Oi, Taiki Higo, Shunsuke Katsuki, Masao Takemoto, Nobuhiro Suematsu, Kenichi Eshima, Kenji Miyata, Mitsutaka Yamamoto, Makoto Usui, Kenji Sadamatsu, Shinji Satoh, Toshiaki Kadokami, Kiyoshi Hironaga, Ikuyo Ichi, Koji Todaka, Junji Kishimoto, Kensuke Egashira, Kenji Sunagawa, Ezetimibe in Combination With Statins Ameliorates Endothelial Dysfunction in Coronary Arteries After Stenting: The CuVIC Trial (Effect of Cholesterol Absorption Inhibitor Usage on Target Vessel Dysfunction After Coronary Stenting), a Multicenter Randomized Controlled Trial., Arteriosclerosis, thrombosis, and vascular biology, 10.1161/ATVBAHA.116.308388, 37, 2, 350-358, 2017.02, OBJECTIVES: We sought to investigate whether treatment with ezetimibe in combination with statins improves coronary endothelial function in target vessels in coronary artery disease patients after coronary stenting. APPROACH AND RESULTS: We conducted a multicenter, prospective, randomized, open-label, blinded-end point trial among 11 cardiovascular treatment centers. From 2011 to 2013, 260 coronary artery disease patients who underwent coronary stenting were randomly allocated to 2 arms (statin monotherapy, S versus ezetimibe [10 mg/d]+statin combinational therapy, E+S). We defined target vessel dysfunction as the primary composite outcome, which comprised target vessel failure during treatment and at the 6- to 8-month follow-up coronary angiography and coronary endothelial dysfunction determined via intracoronary acetylcholine testing performed in cases without target vessel failure at the follow-up coronary angiography. Coadministration of ezetimibe with statins further lowered low-density lipoprotein cholesterol levels (83±23 mg/dL in S versus 67±23 mg/dL in E+S; P
8.	Shunsuke Katsuki, Tetsuya Matoba, Kenji Sunagawa, Kensuke Egashira, Nanoparticle-Mediated Delivery of Pitavastatin Inhibits Atherosclerotic Plaque Destabilization/Rupture in Mice by Regulating the Recruitment of Inflammatory Monocytes, CIRCULATION, 10.1161/CIRCULATIONAHA.113.002870, 129, 8, 896-906, 2014.02, Preventing atherosclerotic plaque destabilization and rupture is the most reasonable therapeutic strategy for acute myocardial infarction. Therefore, we tested the hypotheses that (1) inflammatory monocytes play a causative role in plaque destabilization and rupture and (2) the nanoparticle-mediated delivery of pitavastatin into circulating inflammatory monocytes inhibits plaque destabilization and rupture. We used a model of plaque destabilization and rupture in the brachiocephalic arteries of apolipoprotein E-deficient (ApoE(-/-)) mice fed a high-fat diet and infused with angiotensin II. The adoptive transfer of CCR2(+/+)Ly-6C(high) inflammatory macrophages, but not CCR2(-/-) leukocytes, accelerated plaque destabilization associated with increased serum monocyte chemoattractant protein-1 (MCP-1), monocyte-colony stimulating factor, and matrix metalloproteinase-9. We prepared poly(lactic-co-glycolic) acid nanoparticles that were incorporated by Ly-6G(-)CD11b(+) monocytes and delivered into atherosclerotic plaques after intravenous administration. Intravenous treatment with pitavastatin-incorporated nanoparticles, but not with control nanoparticles or pitavastatin alone, inhibited plaque destabilization and rupture associated with decreased monocyte infiltration and gelatinase activity in the plaque. Pitavastatin-incorporated nanoparticles inhibited MCP-1-induced monocyte chemotaxis and the secretion of MCP-1 and matrix metalloproteinase-9 from cultured macrophages. Furthermore, the nanoparticle-mediated anti-MCP-1 gene therapy reduced the incidence of plaque destabilization and rupture. The recruitment of inflammatory monocytes is critical in the pathogenesis of plaque destabilization and rupture, and nanoparticle-mediated pitavastatin delivery is a promising therapeutic strategy to inhibit plaque destabilization and rupture by regulating MCP-1/CCR2-dependent monocyte recruitment in this model..
9.	Tetsuya Matoba, Kensuke Egashira, Anti-inflammatory gene therapy for cardiovascular disease., Curr Gene Ther, 11, 6, 442-446, 2011.12, [URL], Inflammation in the vascular wall is an essential hallmark during the development of atherosclerosis, for which major leukocytes infiltrated in the lesions are monocytes/macrophages. Therefore, monocyte chemoattractant protein-1 (MCP-1) and its primary receptor CC chemokine receptor 2 (CCR2) are feasible molecular targets for gene therapy to inhibit monocyte/macrophage-mediated inflammation in atherogenesis. A mutant MCP-1 that lacks N-terminal 7 amino acids (7ND) has been shown to heterodimerize with native MCP-1, bind to CCR2 and block MCP-1-mediated monocyte chemotaxis by a dominant-negative manner. Gene therapy using intramuscular transfection with plasmid DNA encoding 7ND showed inhibitory effects on atherosclerosis in hypercholesterolemic mice, and neointima formation after vascular injury in animal models. Bare metal stents for coronary intervention were coated with multiple thin layers of biocompatible polymer with 7ND plasmid. The 7ND gene-eluting stent inhibited macrophage infiltration surrounding stent struts and in-stent neointima formation in rabbit femoral arteries and cynomolgus monkey iliac arteries. Finally, the authors describe new application of 7ND plasmid encapsulated in polymer nanoparticle (NP) that functions as gene delivery system with unique in vivo kinetics. NP-mediated 7ND gene delivery inhibited MCP-1-induced chemotaxis of mouse peritoneal macrophage ex vivo, which may be applicable for the treatment of atherosclerotic cardiovascular disease. In conclusion, anti-inflammatory gene therapy targeting MCP-1/CCR2 signal, with a novel NP-mediated gene delivery system, is a potent therapeutic strategy for the treatment of cardiovascular diseases..

1.	Tetsuya Matoba 1, H. Fujita 2, T. Kohro 3, T. Kabutoya 4, Y. Ohba 4, Y. Imai 4, K. Kario 4, A. Kiyosue 5, Y. Mizuno 5, M. Nakayama 6, K. Nochioka 6, Y. Miyamoto 7, Y. Iwanaga 7, Y. Nakao 7, T. Iwai 7, K. Tsujita 8, T. Nakamura 9, H. Sato 10, Y. Nakano 1, H. Tsutsui 1, R. Nagai 11 (1) Kyushu University, Cardiovascular Medicine, Fukuoka, Japan; (2) Jichi Medical University Saitama Medical Center, Cardiology, Saitama, Japan; (3) Jichi Medical University, Medical Informatics, Tochigi, Japan; (4) Jichi Medical University, Cardiology, Tochigi, Japan; (5) University of Tokyo Hospital, Cardiology, Tokyo, Japan; (6) Tohoku University Graduate School of Medicine, Medical Informatics, Sendai, Japan; (7) National Cerebral and Cardiovascular Center Hospital, Cerebral and Cardiovascular Disease Information, Osaka, Japan; (8) Kumamoto University Hospital, Cardiovascular Center, Kumamoto, Japan; (9) Kumamoto University Hospital, Medical Informatics, Kumamoto, Japan; (10) Precision, Tokyo, Japan; (11) Jichi Medical University, Tochigi, Japan, Clinical Deep Data Accumulation System (CLIDAS) reveals Real-World Medical Therapy and Prognosis of Japanese patients after Percutaneous Coronary Intervention, 日本循環器学会学術集会, 2022.03.
2.	Tetsuya Matoba1, Isashi Baba1, Tomohiro Minakawa2, Yu Sakurai3, Hidetaka Akita3, Jun K. Yamashita2, Hiroyuki Tsutsui1 1 Department of Cardiovascular Medicine, Kyushu University. 2 Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application (CiRA), Kyoto University. 3 Laboratory of Pharmacology and Toxicology, Graduate School of Pharmaceutical Science, Chiba University., Efficacy of microRNA Delivery by Lipid and Polymeric Nanoparticles, Pacifichem 2021, 2021.12.
3.	Tetsuya Matoba, Kazuo Sakamoto, Hiroyuki Tsutsui., Management of Cardiogenic shock in Acute Myocardial Infarction, The 19th International Symposium on Atherosclerosis (ISA 2021), 2021.10, The in-hospital mortality rate of acute myocardial infarction (AMI) has been decreased to 4-5% owing to the spread of coronary care unit (CCU) and the generalization of emergency coronary reperfusion therapy. However, a recent report from the Japanese circulation society (JCS) cardiovascular shock registry (2012-2015), a prospective, observational, multicenter, cohort study that accumulated 979 cardiovascular shock patients among 82 JCS certified teaching hospitals, revealed that the 30-day mortality of acute coronary syndrome (ACS) with cardiogenic shock was as high as 34%, which remains as a challenge in emergency cardiovascular medicine. Management of cardiogenic shock in AMI includes early coronary reperfusion with primary percutaneous coronary intervention (PCI) and mechanical circulatory support; intra-aortic balloon pump, veno-arterial extracorporeal membrane oxygenation, and percutaneous left ventricular assist device (pLVAD or Impella) that had shown the clinical benefit for cardiogenic shock. Since a comprehensive management of cardiogenic shock state as well as early reperfusion therapy is vitally important for the treatment of AMI with cardiogenic shock (Killip class IV), functionally sufficient medical facilities and experienced medical staff are indispensable in order to increase the chance of survival of the patients with Killip class IV AMI. Our recent analysis in the Japanese registry of all cardiac and vascular diseases-diagnosis procedure combination (JROAD-DPC) database (year 2012-2016), 30-day mortality of Killip class IV AMI patients (n=21823) was 42.3%. A multivariate analysis identified age, female gender, admission by ambulance, deep coma, and cardiac arrest as personal factors that were independently associated with higher 30-day mortality, and the number of JCS board certified members as institutional factors that were independently associated with lower mortality in Killip class IV patients. Current guidelines state that patients with suspected STEMI should be transported to a PCI capable center. To further seek better survival of AMI patients with cardiogenic shock, establishing cardiac shock center in the local community may be effective, in which JCS board certified members manage critically ill patients in cooperation with interventional cardiologists, emergency physicians, and intensive care physicians..
4.	Tetsuya Matoba, Gentaro Ikeda, Jun-ichiro Koga, Hiroyuki Tsutsui, Kensuke Egashira, Targeting Cyclophilin D and Inflammation with Nano-medicines in Myocardial Ischemia-Reperfusion Injury, 3rd Annual 2019 International Hawaii Cardiovascular Symposium, 2019.02, Aims: The opening of mitochondrial permeability transition pore (mPTP) and inflammation may cooperatively progress myocardial ischemia-reperfusion (IR) injury; however, clinical trials of cardioprotection with cyclosporine A (CsA) or anti-inflammatory agents ended with neutral results. In this pre-clinical study, we examined the ischemic time-dependent contribution of the 2 mechanisms, and tested the therapeutic effects of nanoparticle-mediated medicine that targets mPTP opening and inflammation in the mouse model of myocardial IR injury. Methods and Results: We employed mice lacking cyclophilin D (CypD, a key molecule for mPTP opening) and CCR2 (a receptor for monocyte chemoattractant protein-1) and found that CypD contributed to progression of myocardial IR injury caused by shorter durations of ischemia (30-45 minutes), whereas CCR2 contributed to IR injury caused by longer durations of ischemia (60-90 minutes). Double deficiency of CypD and CCR2 showed larger cardioprotection over single deficiency regardless of the durations of ischemia. CypD deficiency induced production of interleukin-1β proteins and recruitment of Ly6Chigh inflammatory monocytes in the IR-injured myocardium despite the reduction in the infarction, whereas CCR2-deficiency markedly inhibited these inflammations. Anti-interleukin-1β treatment reduced the recruitment of monocytes to the myocardium, resulted in smaller infarct size in CypD-deficient mice. Then we engineered poly (lactic-co-glycolic acid) nanoparticle containing CsA (CsA-NP) that inhibits mPTP opening and pitavastatin (Pitava-NP) that reduces monocyte-mediated inflammation. Simultaneous treatment with CsA-NP and Pitava-NP at the time of reperfusion presented a remarkable reduction in infarct size after IR injury with 30 or 60 minutes of ischemia. Conclusions: The mechanism of myocardial IR injury differs depending on the durations of ischemia. Simultaneous targeting to mitochondrial injury and inflammation with nano-medicines is a promising strategy that provides a solution for myocardial IR injury..
5.	Tetsuya Matoba, Kazuo Sakamoto, Masahiro Mohri, Yasuyuki Tsujita, Masao Yamasaki, Yasushi Ueki, Nobuhiro Tanaka, Yohei Hokama, Motoki Fukutomi, Katsutaka Hashiba, Rei Fukuhara, Yasushi Ueki, Satoru Suwa, Hirohide Matsuura, Eizo Tachibana, Takahiro Nakashima, Hayato Hosoda, Yoshio Tahara, Michikazu Nakai, Kunihiro Nishimura, Naohiro Yonemoto, Ken Nagao, The Impact of Institutional Characteristics on the Prognosis of Acute Myocardial Infarction with Cardiogenic Shock: Analysis from the JROAD/JROAD-DPC, 日本循環器学会学術集会, 2018.06.