九州大学 研究者情報
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的場 哲哉(まとば てつや) データ更新日:2021.07.21

講師 /  九州大学病院 循環器内科 九州大学大学院医学研究院循環器内科学


主な研究テーマ
冠動脈ステント留置後の冠動脈内皮機能に対する脂質低下療法の効果
キーワード:冠動脈インターベンション、酸化コレステロール、スタチン、エゼチミブ、PCSK9阻害薬
2018.04~2024.03.
循環器疾患リアルワールドデータベースの構築
キーワード:電子カルテ、心臓カテーテル検査、冠動脈インターベンション、SS-MIX、データベース
2017.04~2022.03.
細胞外微粒子の心血管病態における役割の解明と新規治療法の開発
キーワード:エクソソーム、動脈硬化、心筋梗塞
2017.10~2022.03.
動脈硬化性心血管病の病態形成における酸化脂質の役割
キーワード:動脈硬化、酸化コレステロール、血管内皮機能
2011.04~2020.03.
炎症性単球/マクロファージの心血管病における役割の解明と新規治療法の開発
キーワード:炎症 単球 マクロファージ 動脈硬化 急性冠症候群
2012.04~2019.03.
単球選択性ナノ粒子による新規動脈硬化プラーク破綻予防治療の開発
キーワード:動脈硬化 マクロファージ ナノ粒子
2008.04~2011.03.
従事しているプロジェクト研究
クリニカルパスデータの標準化・利活用に係る研究
2018.10~2021.03, 代表者:副島 秀久, 社会福祉法人恩賜財団済生会熊本病院, 医療研究開発推進事業費補助金(日本)
本事業は、日本クリニカルパス学会と日本医療情報学会の合同委員会が主催し、コンセプトは既に広く普及しているもののシステムや運用が標準化されていないクリニカルパス(以下パス)の医療施設・ベンダー間の標準化や相互運用性を進め、複数医療施設に集積したパスデータの統合解析を次世代医療基盤法上で可能とすることを目的とする。まず、収集するデータの解析を志向し、またパス移植性など相互運用性も考慮したパス標準データリポジトリ(以下リポジトリ)規格を定める。リポジトリ規格には、アウトカム・アセスメント(観察項目)・タスクの三層データ構造によるアウトカムユニットを医療工程の最小単位として用い、そのマスターにはHELICS標準化の最終段階である標準アウトカムマスター(以下BOM)の使用を前提とする。次に、実証ターゲットをパスシステムのトップ4ベンダーおよび導入4医療施設とする。リポジトリ規格のデータ構造へデータ出力する標準アウトカム志向型パスシステム(以下標準パスシステム)を各医療施設に導入し、リポジトリおよびその間のインタフェイス(以下IF)を構築する。さらに、複数医療施設から出力されるパスデータの解析基盤を構築する。8種以上の実証用標準的パスを実証医療施設や研究分担者、協力臨床学会等の専門医により策定し、標準パスシステムへ格納し、倫理審査や各医療施設のオーソライズを経て、実入院患者を用いた標準パスシステム実証研究を約1年間行う。蓄積したパスデータをベンチマーク、統合解析するとともに、認定機関により匿名加工情報化しても同様の解析ができることを確認する。実証研究を経て抽出された課題への対策を検討し、標準パスシステム、IF、リポジトリ規格、解析基盤の改修を行う。8種以上の実証用標準的パスも、解析を経て改訂し学会主導の標準パスとする。タスクを含むBOMの改訂、リポジトリ規格のJAHIS標準化を行い、後者はHELICS標準へも申請する。本事業によりベンダー間でパスシステムの標準化が進み、その出力形式やパス移植などの相互運用性が確保されることから、多くの他のパス内容も標準化されるのみならず、パス解析基盤が次世代医療基盤上に構築され、パス活動が活性化と医療の質や効率が劇的に向上することが期待される。アウトカムユニットを中心とした工程管理は次世代電子カルテの技術要素として期待される。.
分化再生と生体恒常性を制御するエクソソームの新しい細胞同調機能の解明とナノ粒子による生体機能制御への応用
2017.10~2022.03, 代表者:山下 潤, 京都大学 iPS細胞研究所, 国立研究開発法人 科学技術振興機構(日本)
分化再生と生体恒常性を制御するエクソソームの新しい細胞同調機能の解明とナノ粒子による生体機能制御への応用.
研究業績
主要原著論文
1. Yasuda S, Kaikita K, Akao M, Ako J, Matoba T, Nakamura M, Miyauchi K, Hagiwara N, Kimura K, Hirayama A, Matsui K, Ogawa H, AFIRE Investigators, Antithrombotic Therapy for Atrial Fibrillation with Stable Coronary Disease., The New England journal of medicine, 10.1056/NEJMoa1904143, 381, 12, 1103-1113, 2019.09, [URL], 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<0.001 for noninferiority). Rivaroxaban monotherapy was superior to combination therapy for the primary safety end point, with event rates of 1.62% and 2.76% per patient-year, respectively (hazard ratio, 0.59; 95% CI, 0.39 to 0.89; P=0.01 for superiority). CONCLUSIONS As antithrombotic therapy, rivaroxaban monotherapy was noninferior to combination therapy for efficacy and superior for safety in patients with atrial fibrillation and stable coronary artery disease..
2. 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, 1244-1255, 2019.06, [URL], Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com. 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..
3. 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, [URL], 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..
4. 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, 419-431, 2019.02, [URL], © 2018 Published on behalf of the European Society of Cardiology. All rights reserved. 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 Ly6C high 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..
5. 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, Arteriosclerosis, Thrombosis, and Vascular Biology, 10.1161/ATVBAHA.117.310244, 38, 4, 757-771, 2018.04, 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..
6. 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-+, 2017.02, [URL], 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<0.0001), with significant decreases in oxidized low-density lipoprotein and oxysterol levels. Among patients without target vessel failure, 46 out of 89 patients (52%) in the S arm and 34 out of 96 patients (35%) in the E+S arm were found to have coronary endothelial dysfunction (P=0.0256), and the incidence of target vessel dysfunction at follow-up was significantly decreased in the E+S arm (69/112 (62%) in S versus 47/109 (43%) in E+S; P=0.0059). A post hoc analysis of post-treatment low-density lipoprotein cholesterol-matched subgroups revealed that the incidence of both target vessel dysfunction and coronary endothelial dysfunction significantly decreased in the E+S arm, with significant reductions in oxysterol levels.
Conclusions-The CuVIC trial (Effect of Cholesterol Absorption Inhibitor Usage on Target Vessel Dysfunction after Coronary Stenting) has shown that ezetimibe with statins, compared with statin monotherapy, improves functional prognoses, ameliorating endothelial dysfunction in stented coronary arteries, and was associated with larger decreases in oxysterol levels..
7. 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..
8. 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..
主要総説, 論評, 解説, 書評, 報告書等
主要学会発表等
1. 26. 的場哲哉、古賀 純一郎、香月 俊輔、内川 智貴、馬場 功士、江頭 健輔、筒井 裕之, 酸化ステロールの炎症と老化における役割, 第52回日本動脈硬化学会総会, 2020.07.
2. 的場哲哉1、興梠貴英2、藤田英雄2、中山雅晴3、清末有宏4、橋本英樹4、大江和彦4、宮本恵宏5、西村邦宏5、小川久雄5、安徳恭彰1、中島直樹1、筒井裕之1、永井良三2 1九州大学、 2自治医科大学、 3東北大学、 4東京大学、 5国立循環器病研究センター;日本循環器学会IT/Database委員会 , 心臓カテーテルを中心とした多モダリティ循環器診療情報を収集するJ-IMPACTシステム, 第38回医療情報学連合大会(第19回日本医療情報学会学術大会), 2019.06, 循環器疾患は心筋梗塞、脳卒中を代表とした血管病により日本人の生活の質を損ねる重大な疾患領域である。特徴的に発展した心臓カテーテル検査・心臓カテーテルインターベンション治療の診療情報、また、大規模臨床試験のエビデンスに基づく薬物療法などの診療情報などは、構造化データとして個別患者のリスク予測や治療プロセスの再評価に利用されるべきであるが、多モダリティの診療情報を電子的に収集するシステムは存在しなかった。我々は日本循環器学会およびImPACT事業の支援を受け、電子カルテにおける患者基本情報、処方、検体検査データをSS-MIX2標準ストレージから、また、生理検査や心臓カテーテル検査・心臓カテーテルインターベンション治療レポートの情報をSS-MIX2拡張ストレージから収集するJapan Ischemic Heart Disease Multimodal Prospective Data Acquisition for Precision Treatment (J-IMPACT)システムを開発してきた。本発表ではJ-IMPACTシステムの現状と課題を議論したい。
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3. 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. .
4. 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.
5. Tetsuya Matoba, Kaku Nakano, Kenji Sunagawa, Kensuke Egashira, Nanoparticle-Mediated Monocyte-Selective Drug Delivery System for Treatment of Atherosclerotic Cardiovascular Disease, Cardiovascular System Dynamics Society 2010, 2010.09.
学会活動
所属学会名
日本動脈硬化学会
日本不整脈学会
日本血管生物医学会
米国心臓協会
日本心血管インターベンション学会
日本循環器学会
日本内科学会
学協会役員等への就任
2018.04~2022.03, 日本循環器学会, Fellow (FJCS).
2018.01~2021.12, European Society of Cardiology, Fellow (FESC).
2014.04~2020.03, 国際心血管薬物療法学会日本部会, 評議員.
2014.04~2022.03, 日本心血管インターベンション治療学会, 評議員.
2013.07~2020.07, 日本動脈硬化学会, 評議員.
2013.05~2023.05, American Heart Associatioin, International Fellow of AHA.
2010.04~2020.03, 日本循環器学会九州地方会, 評議員.
2021.02~2024.03, 日本血管生物医学会, 理事.
学会大会・会議・シンポジウム等における役割
2019.01.25~2019.01.26, 画像動体学会, 座長.
2018.12.06~2018.12.08, ISHR 国際心臓研究会, 座長.
2018.10.11~2018.10.13, APCHF , 座長.
2018.09.22~2018.09.23, BCVR 日本循環器学会基礎研究シンポジウム, 座長.
2018.06.30~2018.06.30, 日本循環器学会九州地方会, 座長.
2018.04.23~2018.04.23, 福博循環器セミナー, 座長.
2017.04.14~2017.04.14, Bifurcation symposium, 座長(Chairmanship).
2017.03.04~2017.03.04, 日本老年医学会九州地方会, 座長(Chairmanship).
2016.08.19~2016.08.20, 日本心血管インターベンション学会九州沖縄地方会, 座長(Chairmanship).
2016.06.25~2016.06.25, 日本循環器学会九州地方会, 座長(Chairmanship).
2017.03.17~2017.03.19, 日本循環器学会総会, 座長(Chairmanship).
2015.04.23~2015.04.26, 日本循環器学会, 座長(Chairmanship).
2014.10.24~2014.10.24, QcVIC Research, 座長(Chairmanship).
2014.07.10~2014.07.11, 日本動脈硬化学会, 座長(Chairmanship).
2014.06.28~2014.06.28, 日本循環器学会九州地方会, 座長(Chairmanship).
2014.06.27~2014.06.27, QcVIC Research, 座長(Chairmanship).
2013.07.18~2013.07.20, 日本動脈硬化学会, 座長(Chairmanship).
2013.02.23~2013.02.23, 第7回QcVIC, 座長(Chairmanship).
2012.09.29~2012.09.29, 第6回QcVIC, 座長(Chairmanship).
2012.09.07~2012.09.09, Molecular Cardiovascular Conference II, 座長(Chairmanship).
2012.07.19~2012.07.20, 日本動脈硬化学会, 座長(Chairmanship).
2010.09.04~2010.09.05, Molecular Cardiovascular Conference II, 座長(Chairmanship).
2014.11.29~2014.11.29, QcVIC, 世話人.
2014.09.05~2014.09.06, Molecular Cardiovascular Conference II, 世話人.
2011.09.02~2011.09.04, Molecular Cardiovascular Conference II, 世話人、座長.
2009.09~2015.09, Molecular Cardiovascular Conference II, 世話人.
学会誌・雑誌・著書の編集への参加状況
2015.04~2017.04, International Heart Journal, 国際, 編集委員.
学術論文等の審査
年度 外国語雑誌査読論文数 日本語雑誌査読論文数 国際会議録査読論文数 国内会議録査読論文数 合計
2020年度 31        31 
2019年度 22        22 
2018年度 24        24 
2017年度 20  20 
2016年度 25        25 
2015年度 29        29 
2014年度 10        10 
2013年度    
2012年度      
2011年度      
2010年度      
その他の研究活動
海外渡航状況, 海外での教育研究歴
Cardiovascular Research Institute, University of Rochester Medical Center, UnitedStatesofAmerica, 2003.09~2006.03.
受賞
ATVB Travel Grant, 2008.11.
第15回五島雄一郎賞, 日本動脈硬化学会, 2019.07.
Circulation Journal Best Reviewers Award, 日本循環器学会, 2017.03.
Young Investigator Award, 日本循環器学会, 2003.03.
研究資金
科学研究費補助金の採択状況(文部科学省、日本学術振興会)
2021年度~2024年度, 基盤研究(B), 代表, 心血管の炎症における酸化ステロールの分子生物学的役割と治療標的の解明.
2017年度~2019年度, 基盤研究(C), 代表, 急性心筋梗塞後の心臓修復を促進する革新的PPARγナノ医薬の研究開発.
2007年度~2008年度, 若手研究(B), 代表, 動脈硬化プラーク破綻におけるマクロファージ・アポトーシスの役割解明と治療法.
2009年度~2010年度, 若手研究(B), 代表, マクロファージ分化スイッチ制御による粥状動脈硬化プラーク破綻予防療法の研究開発.
科学研究費補助金の採択状況(文部科学省、日本学術振興会以外)
2021年度~2023年度, 厚生労働科学研究費補助金 (厚生労働省), 分担, 標準化クリニカルパスに基づく、医師行動識別センサや問診AIなどのICTを用いた医師の業務負担軽減手法に関する研究.
2017年度~2019年度, AMED: JROAD・J-ASPECT・脳卒中データバンクによる全国規模レジストリーによる脳卒中および循環器疾 患の実態把握の確立と両疾患合併例に関する包括的診療実態解明, 分担, JROAD・J-ASPECT・脳卒中データバンクによる全国規模レジストリーによる脳卒中および循環器疾 患の実態把握の確立と両疾患合併例に関する包括的診療実態解明.
2017年度~2019年度, 厚生労働科学研究費補助金 (厚生労働省), 分担, 研究項目:SS-MIX2データ抽出システム実装とテストおよびアウトカムテンプレート仕様検討
.
2014年度~2014年度, 厚生労働科学研究費補助金 (厚生労働省), 分担, 重症肺高血圧症の予後と生活の質を改善するための安心安全のナノ医療製剤(希 少疾病用医薬品)の実用化臨床試験.
日本学術振興会への採択状況(科学研究費補助金以外)
2017年度~2022年度, 戦略的創造研究推進事業・CREST, 分担, 分化再生と生体恒常性を制御するエクソソームの新しい細胞同調機能の解 明とナノ粒子による生体機能制御への応用.
競争的資金(受託研究を含む)の採択状況
2008年度~2009年度, ストラゼネカ・リサーチ・グラント, 代表, New therapeutic approach to control atherosclerotic cardiovascular disease.

九大関連コンテンツ

pure2017年10月2日から、「九州大学研究者情報」を補完するデータベースとして、Elsevier社の「Pure」による研究業績の公開を開始しました。
 
 
九州大学知的財産本部「九州大学Seeds集」