Elucidation of a novel pathogenic mechanism of heart failure progression mediated by trimeric G protein

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K17077
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53020:Cardiology-related
• Research Institution: Kyoto University
• Principal Investigator: Inazumi Hideaki 京都大学, 医学研究科, 医員 (10844037)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 心不全

Outline of Final Research Achievements

By analyzing a proprietary mouse model of heart failure, we have discovered that Gαo, a subtype of the inhibitory G protein α subunit (Gαi/o) family, whose role in cardiovascular disease has not been clarified, is upregulated in failing ventricular muscle and contributes to the onset and progression of heart failure. In this study, we found that Gαo up-regulation alters the localization of L-type Ca channel currents in mouse ventricular myocytes (L-type Ca channel currents through the cell surface membrane, not T-tube, are increased) as a molecular mechanism. We also found that this was not due to the subcellular localization of L-type Ca channels but to changes in their activity.

Free Research Field

循環器内科学

Academic Significance and Societal Importance of the Research Achievements

私達はこれまで心血管病における役割が明らかでなかった抑制性Gタンパクサブユニット(Gαi/o)ファミリーのサブタイプの一つであるGαoが心筋細胞内のL型Caチャネルの局所活性を変化させることで心不全の発症・進展に寄与するという新知見を見出すことができました。本研究成果は高齢化により今後ますます増加が見込まれる心不全患者さんに対する新たな治療法の開発に繋がる可能性があると考えられます。