Elucidation of regulatory mechanisms of mitochondrial function in failing heart by Tim44 and its therapeutic application.

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K16026
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53020:Cardiology-related
• Research Institution: Kyushu University
• Principal Investigator: Ikeda Soichiro 九州大学, 医学研究院, 共同研究員 (00885410)
• Project Period (FY): 2021-04-01 – 2023-03-31
• Keywords: 心不全 / 心筋リモデリング / ミトコンドリア / 酸化ストレス / 細胞死

Outline of Final Research Achievements

In failing hearts after myocardial infarction　(MI), Tim44 was decreased compared to sham-operated mice. In cardiomyocytes, Tim44 was decreased by administration of H2O2. Heterozygous Tim44 knockout （KO） mice did not show cardiac dysfunction at baseline. After MI, heterozygous Tim44 KO mice exhibited cardiac dysfunction compared with WT mice. Overexpression of Tim44 in cardiomyocytes ameliorated H2O2-induced cell death in cardiomyocytes. These results suggest that, in failing hearts after MI, the decrease in Tim44 is related to cardiomyocytes death and cardiac dysfunction and overexpression of Tim44 prevents cardiac dysfunction by attenuating cardiomyocytes death.

Free Research Field

循環器内科学

Academic Significance and Societal Importance of the Research Achievements

本研究は不全心おけるミトコンドリア機能障害の機序解明やTim44の役割の解明を行うことで心不全および心筋リモデリングの病態基盤の解明を明らかにするとともに、機序解明により新規治療法の開発に発展する可能性がある。