Basic research for the development of innovative therapeutic approaches against heart failure

2020 Fiscal Year Final Research Report

• Project/Area Number: 18H02809
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 53020:Cardiology-related
• Research Institution: Kumamoto University
• Principal Investigator: OIKE Yuichi 熊本大学, 大学院生命科学研究部(医), 教授 (90312321)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 心不全 / ミトコンドリア / エネルギー代謝

Outline of Final Research Achievements

In this study, we showed a molecular mechanism underlying the enhancement of mitochondrial energy metabolism in cardiomyocytes by ANGPTL2 suppression. Suppressing ANGPTL2 expression in cardiomyocytes enhances mitochondrial respiratory function by increasing the respiratory chain complex II and decreases the production of reactive oxygen species. Moreover, we identified a novel lncRNA Caren and demonstrated that Caren functions in cardioprotection by enhancing mitochondrial biogenesis and inhibiting the activation of DNA damage response in cardiomyocytes. We also found that the expression level of Caren decreases in cardiomyocytes of failing heart and showed that re-expression of Caren in cardiomyocytes could be a novel therapeutic strategy against heart failure.

Free Research Field

代謝・循環病態学、分子遺伝学

Academic Significance and Societal Importance of the Research Achievements

本研究の成果として、心筋細胞におけるミトコンドリアエネルギー代謝機能の改善が、心不全の新たな治療戦略として有効であることを明らかにするなど、新規治療法開発につながる重要な基盤研究となった。さらに、本研究の成果は、心筋細胞におけるミトコンドリアエネルギー代謝機能制御機構として、ANGPTL2抑制による呼吸鎖複合体IIの活性促進や新規lncRNAであるCarenによるミトコンドリア生合成促進などの作用機序の解明といった学術的意義も有する。