Improvement of therapeutic methods for cardiomyopathy/heart failure based on the functional analysis of stretch-activated ion channel

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Dilated cardiomyopathy (DCM) is a severe disorder defined by ventricular dilation and cardiac dysfunction. A subset of familial DCM is caused by mutations of the genes encoding cytoskeleton. Here, we show that transient receptor potential vanilloid 2 (TRPV2) is highly concentrated in the ventricular sarcolemma of patients with idiopathic DCM and animal models of cardiomyopathy. We found some tools to inhibit the surface expression of and Ca2+ influx via TRPV2. In the animal models, blockade of TRPV2 ameliorated cardiac dysfunction, and prevented DCM progression; Therefore, we propose that sarcolemmal accumulation or activation of TRPV2 initiated by membrane instability resulting from cytoskeleton abnormalities contributes to cardiac dysfunction in DCM, and TRPV2 may be a promising therapeutic target for advanced heart failure.