Elucidation of the mechanism of heart failure involving mitochondrial DNA accumulation

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K17079
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53020:Cardiology-related
• Research Institution: Osaka University
• Principal Investigator: Ueda Hiromichi 大阪大学, 医学系研究科, 助教 (30865746)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: ミトコンドリアDNA

Outline of Final Research Achievements

With regard to DNase II, an enzyme that degrades mitochondrial DNA, which is found to accumulate in cardiomyocytes in heart failure, it has been clarified that the decrease in activity is due to the decrease in gene expression level. Based on a hypothesis that the gene expression is regulated by some microRNAs, we identified the candidates and confirmed that these candidates exist in human myocardial tissue of heart failure. The prophylactic effect of heart failure by lowering microRNA and enhancing the activity of DNase II was studied, but it was not enough to confirm its sufficient effect.

Free Research Field

心不全

Academic Significance and Societal Importance of the Research Achievements

心筋症や心不全においても認められる炎症は病態形成において重要な役割を果たすが、本仮説（ミトコンドリアDNA蓄積に由来する無菌的な自然免疫応答がこの病態の一因である）に基づいたまったく新しい心不全治療戦略を検討した。ミトコンドリアDNA分解に関わる分子（DNaseII）の心臓での発現動態を理解しこれを制御することにより、心臓の炎症制御から心不全を予防することを目指し、動物モデルを用いて本仮説の検証をおこなった。