The investigation of the role of protein degradation pathway during progression to heart failure, and the application to heart failure treatment.

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We investigated the role of calpain pathway which is known as a protein degradation pathway in the pathogenesis of heart failure using cardiac-specific calpain4-deficient mice. We found the increase in apoptotic cardiomyocyte death in deficient mice in response to pressure overload, leading to cardiac dilatation and decreased cardiac contractility. Thus, we concluded that calpain pathway in the heart plays a protective role in response to pressure overload mediated through the inhibition of stress-induced cardiomyocyte apoptosis.