Development of new treatments for cardiomyopathy and heart failure targeting mechanosensor channels

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K08462
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53020:Cardiology-related
• Research Institution: National Cardiovascular Center Research Institute
• Principal Investigator: Iwata Yuko 国立研究開発法人国立循環器病研究センター, 研究所, 非常勤研究員 (80171908)
• Co-Investigator(Kenkyū-buntansha): 泉 知里 国立研究開発法人国立循環器病研究センター, 病院, 部門長 (70768100) ; 伊藤 慎 国立研究開発法人国立循環器病研究センター, 病院, 室長 (20796560)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 心不全

Outline of Final Research Achievements

To clarify the pathophysiological significance of the calcium-permeable channel TRPV2 in cardiomyopathy and heart failure, and to determine its potential as a therapeutic target, TRPV2 activation was inhibited in animal models of myocardial ischemia-reperfusion injury and aortic banding-induced heart failure, resulting in a suppression of onset and progression of these conditions. Additionally, the effectiveness of a TRPV2 inhibitor was investigated in advanced-stage heart failure muscular dystrophy patients, with a significant difference observed in the rate of change of BNP, a serum marker of heart failure. While the surface expression of TRPV2 on monocytes and PGD2 metabolites in urine were increased in muscular dystrophy patients, they were found to decrease after 4 and 12 weeks of drug administration, indicating that TRPV2 inhibitors have an inhibitory effect on inflammation associated with heart failure.

Free Research Field

分子生理学

Academic Significance and Societal Importance of the Research Achievements

研究結果は、TRPV2が心筋症・心不全の病態生理に関与していることを示唆している。さらに、TRPV2を抑制することで心筋虚血再灌流傷害や大動脈狭窄心不全の発症及び進展が抑制されることが判明した。また、TRPV2阻害薬が心不全に伴う炎症を抑制する作用があることも示されたため、将来的にはTRPV2を治療標的とした心筋症・心不全の治療法が開発される可能性が高い。