The molecular mechanism of myocardial fibrosis in ventricular remodeling after myocardial infarction

• Project/Area Number: 17K09271
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Legal medicine
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: Shintani-Ishida Kaori 京都府立医科大学, 医学(系)研究科(研究院), 准教授 (50345047)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 心不全 / 心筋梗塞 / カルパイン / 虚血再灌流 / TGF-β1 / リモデリング / 急性心筋梗塞 / 心室リモデリング / ペントラキシン3 / 線維化

Outline of Final Research Achievements

The aim of this study was to clarify the mechanism of myocardial fibrosis, which is a critical feature of ventricular remodeling after myocardial infarction. We investigated whether a proteinase calpain is involved in transforming growth factor (TGF)-β1-mediated myocardial fibrosis in a rat myocardial infarction model. Calpain was activated on coronary artery smooth muscle immediately after ischemia-reperfusion and induced TGF-β1 expression. Calpain decreased the level of miRNA-133a, which suppresses TGF-β1 expression. These results suggested a new role of calpain as a modulator of miRNA expression in TGF-β1-mediated myocardial fibrosis.

Academic Significance and Societal Importance of the Research Achievements

心不全は罹患率が高く、突然死を引き起こすこともある。心不全は心筋梗塞後に発症することが多く、その機序を明らかにすることは治療や予防に重要である。本研究では心筋梗塞後に活性化するタンパク質分解酵素カルパインが心筋梗塞後の心不全発症にどのように関与しているかを動物モデルを用いて検討した。その結果、カルパインはタンパク質の発現量を制御するmiRNAの量を調節し、TGF-β1という心筋線維化を引き起こす因子を増加させるという、これまで知られていなかった新しい役割を見出した。

Research Products

• [Journal Article] Simple, Frequent Indicator for Personal Identification?Postmortem and Antemortem Abdominal Computed Tomography Findings of a Charred Body (2020)
  • Author(s): Nakamura Mami、Idota Nozomi、Shintani-Ishida Kaori、Hitosugi Masahito、Ikegaya Hiroshi
  • Journal Title: The American Journal of Forensic Medicine and Pathology Volume: 41 Issue: 1 Pages: 56-59
  • DOI: 10.1097/paf.0000000000000522
  • Peer Reviewed
• [Journal Article] Postmortem plasma pentraxin 3 is a useful marker of fatal acute coronary syndrome (2019)
  • Author(s): Tojo Misa、Shintani-Ishida Kaori、Tsuboi Hajime、Nakamura Mami、Idota Nozomi、Ikegaya Hiroshi
  • Journal Title: Scientific Reports Volume: 9 Issue: 1
  • DOI: 10.1038/s41598-019-44472-0
  • Peer Reviewed / Open Access
• [Journal Article] Autoerotic asphyxia using a plastic bag loosely covering the head over a gas mask (2019)
  • Author(s): Idota Nozomi、Nakamura Mami、Tsuboi Hajime、Ichioka Hiroaki、Shintani-Ishida Kaori、Ikegaya Hiroshi
  • Journal Title: Legal Medicine Volume: 38 Pages: 69-72
  • DOI: 10.1016/j.legalmed.2019.04.006
  • Peer Reviewed
• [Presentation] Ischemia-reperfusion induces calpain-1 activation in smooth muscle cells of coronary arteries via angiotensin II/TGF-β1. (2019)
  • Author(s): Shintani-Ishida K, Yoshida K.
  • Organizer: 第83回日本循環器学会学術集会
• [Presentation] 薬物スクリーニング検査における異機種並行分析の意義． (2019)
  • Author(s): 新谷 香，鶴海 莉子，坂東 李紗，市岡 宏顕，坪井 創，井戸田 望，池谷 博．
  • Organizer: 第66回日本法医学会学術近畿地方集会
• [Presentation] Ischemia-reperfusion induces calpain-1 activation in smooth muscle cells of coronary arteries via angiotensin II/TGF-β1 (2019)
  • Author(s): Shintani-Ishida K, Yoshida K
  • Organizer: 第83回日本循環器学会学術集会
• [Remarks] 京都府立医科大学法医学教室ホームページ
  • URL: http://www.f.kpu-m.ac.jp/k/hoi/