2021 Fiscal Year Final Research Report
Mitochondrial dynamics in myocardial ischemia-reperfusion injury and post-infarct remodeling
Project/Area Number |
19K08518
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 53020:Cardiology-related
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Research Institution | Kyushu University |
Principal Investigator |
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Project Period (FY) |
2019-04-01 – 2022-03-31
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Keywords | マクロファージ / 心筋梗塞後リモデリング / ミトコンドリアダイナミクス / マイトファジー |
Outline of Final Research Achievements |
Mitochondria consistently change their morphology, which is closely related to cellular functions. In this study, we focused on the role of Drp1 (dynamin-related protein 1), which promotes mitochondrial division, in macrophages accumulating in the heart after myocardial infarction. For this purpose, we used Lysozyme-M-positive cells-specific Drp1-deficient mice. There was no significant difference in myocardial infarct size between these mice and control mice after transient occlusion of the anterior descending left coronary artery (LAD). In contrast, the deletion of Drp1 exacerbated inflammation and left ventricular enlargement after permanent occlusion of LAD compared to control mice. These results suggest that long-term inhibition of mitochondrial fission after myocardial infarction may promote the accumulation of damaged mitochondria, inflammation, and left ventricular remodeling. Further investigation is needed to clarify the detailed mechanism.
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Free Research Field |
循環器内科学
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Academic Significance and Societal Importance of the Research Achievements |
本研究によりこれまで不明であったマクロファージDrp1が急性心筋梗塞の病態において果たす役割が明らかとなった。心筋梗塞後の左室リモデリングは慢性期に繰り返す心不全の原因となり患者の生活の質(quality of life)、生命予後に及ぼす影響も大きく、その分子メカニズム解明と新規予防法、治療法の開発が求められている。本研究の成果はミトコンドリアダイナミクスへの介入を通じた新規治療開発に向けた第一歩となりうるが、ミトコンドリアは細胞内において多様な機能を担っており、副作用の少ない治療開発のためにはさらなる分子メカニズムの解明と適切な標的分子の選択が必要である。
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