Significance of DNA damage response in inflammation during remodeling after myocardial infarction

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K08038
• 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: Hiroshima University
• Principal Investigator: ISHIDA Mari 広島大学, 医系科学研究科(医), 准教授 (30359898)
• Co-Investigator(Kenkyū-buntansha): 石田 隆史 福島県立医科大学, 医学部, 教授 (40346482)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: DNA損傷 / 炎症 / マクロファージ / 心筋梗塞 / 線維化 / 心不全

Outline of Final Research Achievements

The remodeling that occurs after myocardial infarction has a major impact on the development of heart failure. We examined whether the DNA damage response is important for the inflammatory response in remodeling after myocardial infarction.
When myocardial infarction occurred in Ku80 knockout mice, which exhibit an abnormal DNA damage response, compared to wild-type mice, we observed reduced cardiac function, worse prognosis, increased myocardial DNA damage, delayed expression of proinflammatory cytokines, reduced accumulation of M2 macrophages at the infarct area, reduced differentiation to M2a. These results suggest that the DNA damage response is important for macrophage differentiation and dynamics and inflammatory response during myocardial infarction, and influences cardiac remodeling.

Free Research Field

循環器内科学

Academic Significance and Societal Importance of the Research Achievements

炎症が損傷した心筋の修復・リモデリング機転に深く関わることは知られているが、本研究によりその炎症・抗炎症のバランスにDNA損傷応答が重要であることが示された。本研究の成果により、心筋梗塞時のDNA損傷応答を制御することにより炎症とその結果としての心リモデリング、心機能の低下を抑制する新しい治療法の開発が可能であると考えられた。