JOURNAL ARTICLE
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Genetic and epigenetic regulation of arrhythmogenic cardiomyopathy.

Arrhythmogenic cardiomyopathy (AC) is most commonly characterized as a disease of the intercalated disc that promotes abnormal cardiac conduction. Previously, arrhythmogenic cardiomyopathy was frequently referred to as arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D); however, genotype-phenotype studies have defined a broader phenotypic spectrum; with the identification of left-dominant and biventricular subtypes. Molecular insight into AC has primarily focused on mutations in desmosomal proteins and the downstream signaling pathways; however, desmosomal gene mutations can only be identified in approximately 50% of patients with AC. Animal and cellular studies have shown that in addition to abnormal biomechanical properties from changes in desmosome function, crosstalk from the desmosome to the nucleus, gap junctions, and ion channels are implicated in the pathobiology of AC. In this review, we highlight some of the newly identified genetic and epigenetic mechanisms that may lead to the development of AC including the role of the Hippo pathway and microRNAs. This article is part of a Special Issue entitled: Genetic and epigenetic control of heart failure - edited by Jun Ren & Megan Yingmei Zhang.

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