The contribution of extracellular nucleotides and vesicles to the progression of atrial fibrillation

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K08536
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53020:Cardiology-related
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Sasano Tetsuo 東京医科歯科大学, 大学院医歯学総合研究科, 教授 (00466898)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 心房細動 / 細胞外核酸 / 細胞外小胞 / cell-free DNA / バイオマーカ

Outline of Final Research Achievements

We investigated the intercellular communication mediated by extracellular nucleic acids and extracellular vesicles in atrial fibrillation (AF), and assess its relation to the progression of AF. When atrial myocytes had high -frequency electrical stimulation, specific extracellular vesicles were released into the culture medium, which induced an inflammatory response in adipocytes. We also demonstrated that this response was enhanced in the presence of macrophages.
Furthermore, we developed a method to directly quantify the particle size and particle number of extracellular vesicles in plasma without the process of vesicle extraction. Applying this method, we revealed an increase in extracellular vesicles in peripheral blood in arrhythmias such as atrial fibrillation and premature ventricular contractions. We also found that these vesicles induced distinct changes in target cells, such as vascular endothelial cells.

Free Research Field

循環器内科学

Academic Significance and Societal Importance of the Research Achievements

心房細動は本邦で診断されている患者数が90万人、発症しているが診断にはいたっていないと推定される患者数を合わせると約200万人になる。心房細動の最大の合併症は心原性脳塞栓であり、日本の寝たきりの約20%が心原性脳塞栓という報告もあることから、心房細動の病態の解明や早期介入への知見は非常に社会的意義の高いものといえる。
また本研究では、心房筋から放出される細胞外核酸や細胞外小胞に着目した研究であり、なぜ多くの不整脈疾患の中で心房細動のみが多彩な全身性合併症を生じるのか、という問いに答えるもので、学術的意義も高い。