2023 Fiscal Year Final Research Report
Elucidation of an autonomous and self-amplifying mechanism to explain the increased incidence and chronicity of atrial fibrillation in the elderly
| Project/Area Number |
21H02909
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 53020:Cardiology-related
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
井原 健介 東京医科歯科大学, 難治疾患研究所, 助教 (50770210)
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Keywords | 心房細動 / ミトコンドリア / セルフリーDNA / バイオマーカー |
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| Outline of Final Research Achievements |
Atrial fibrillation (AF) is the most common type of arrhythmia and is a major social issue in Japan as it frequently leads to cardioembolic stroke and accounts for approximately 20% of bedridden patients. In this clinical trial, we found that circulating mitochondrial DNA (mtDNA) levels were higher in patients with chronic AF than in healthy controls and patients with paroxysmal AF. In vitro and in vivo experiments using cultured cells and mice, we demonstrated that high-frequency stimulation induces the release of mitochondrial DNA (mtDNA) as a DAMP and that mtDNA triggers an inflammatory response via TLR9. These findings suggest that mtDNA links metabolic stress and inflammation, contributing to the development and progression of atrial fibrillation (AF).
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| Free Research Field |
循環器内科
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| Academic Significance and Societal Importance of the Research Achievements |
心房細動はもっと頻度の多い不整脈であり、高頻度に脳梗塞（心原性脳塞栓）を合併し、本邦における寝たきりの約20%の原因となっている喫緊の社会程課題となっている。今回、循環ミトコンドリアフリーDNAが心房細動発症、及び慢性化のバイオマーカーとなること、そのメカニズムを明らかにしたことが学術的に高く評価できる。
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