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2022 Fiscal Year Final Research Report

Novel role of small G protein signaling in the cardiac senescence-induced heart dysfunction

Research Project

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Project/Area Number 20K08489
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 53020:Cardiology-related
Research InstitutionShiga University of Medical Science

Principal Investigator

Ogita Hisakazu  滋賀医科大学, 医学部, 教授 (50379236)

Project Period (FY) 2020-04-01 – 2023-03-31
Keywords心機能 / ミトコンドリア / 老化 / RhoA
Outline of Final Research Achievements

The main findings of this study were the cardioprotective effects of RhoA, a small GTPase, on cardiac senescence, which was certified by use of the originally generated cardiomyocyte-specific RhoA conditional knockout (cKO) mice. RhoA promoted the expression of Parkin in cardiomyocytes, and maintained the function of mitochondria in the heart. When reduced Parkin expression in the RhoA cKO heart was supplemented by the adeno-associated virus (AAV) system, cardiac senescence was almost completely recovered.

Free Research Field

生化学、循環器内科

Academic Significance and Societal Importance of the Research Achievements

学術的意義として、高齢者で増加している心機能低下、心不全に関する新たな分子メカニズムを解明することができた。心不全は現在でも5年生存率約50%という予後不良の病態であり、本研究の成果は超高齢社会の日本においてこの病態を克服するための治療法開発の基盤として活用できる。例えば、心筋RhoAの発現が低下している心不全患者に対して、AAVを用いて心筋へのRhoAあるいはパーキンの補充療法を開発していくことなどが考えられる。

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Published: 2024-01-30  

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