The Amount of Autophagy-Related Cardiomyocyte Cell Death Is Associated With the Type of Pathogenic Mutation in Genetic Dilated Cardiomyopathy

Abstract

Genetic dilated cardiomyopathy is a heterogenous group of diseases caused by mutations in various genes. Progressive cardiomyocyte loss and subsequent fibrosis is a key feature of this disease. Several types of cardiomyocyte cell death have been implicated: (macro) autophagy-related cell death, apoptosis, necroptosis and oncosis. One plausible mechanism of genetic cardiomyopathy is proteotoxicity of accumulated mutant protein aggregates. Here we investigate the association of such aggregates as a sign of autophagy-related cardiomyocyte cell death with specific pathogenic mutations in dilated cardiomyopathy.