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

扩张型心肌病（DCM）是一种严重的疾病，定义为心室扩张和心功能不全。家族性DCM的一个子集是由编码细胞骨架的基因突变引起的。在这里，我们表明，瞬时受体电位香草酸2（TRPV 2）是高度集中在心室肌膜的特发性扩张型心肌病患者和心肌病动物模型。我们发现了一些抑制TRPV 2表面表达和Ca 2+内流的工具。在动物模型中，阻断TRPV 2可改善心功能障碍，并阻止DCM进展;因此，我们认为，由细胞骨架异常引起的膜不稳定引发的TRPV 2的肌膜积聚或激活有助于DCM的心功能障碍，TRPV 2可能是晚期心力衰竭的有希望的治疗靶点。

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.