Mechanism of the effect of reactive oxygen species on cardiac diastolic dysfunction

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K16013
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 47040:Pharmacology-related
• Research Institution: Toho University
• Principal Investigator: HAMAGUCHI Shogo 東邦大学, 薬学部, 講師 (80747767)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 酸化ストレス / 拡張機能障害 / SERCA

Outline of Final Research Achievements

This study focused on the relationship between oxidative stress and diastolic dysfunction, a type of heart failure. Among natural products with antioxidant activity, ellagic acid, gingerol, and quercetin were found to shorten relaxation time in mouse isolated ventricular tissue preparations. These relaxation time shortening effects were also observed in a diabetic mouse model of diastolic dysfunction. The mechanism of action was suggested to be the enhancement of Ca2+ uptake by the sarcoplasmic reticulum Ca2+ pump and correction of intracellular Ca2+ dynamics, which may be helpful for the treatment of diastolic dysfunction.

Free Research Field

循環薬理学

Academic Significance and Societal Importance of the Research Achievements

従来、心不全は心ポンプ機能のうち駆出機能に焦点が当てられ、収縮機能の低下が病態の主体であると考えられてきた。しかし、心収縮力機能低下を伴わない拡張機能障害に基づく心不全の患者数は近年増加傾向にあり、糖尿病、高血圧、加齢などが増悪因子となる。このタイプの心不全の治療では、高血圧の是正やうっ血軽減を目的として利尿薬や血管拡張薬が用いられるが、病態の根底にある拡張機能の改善に焦点をあてた治療薬は存在しない。したがって、心筋の拡張メカニズムの詳細な解明と拡張機能をターゲットとした薬物の創出は、拡張機能障害の新たな治療戦略の開発に繋がると考えられる。