Murine models of ARVC: what have we learned and where do we go? Insight for therapeutics.

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Abstract

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a rare genetically-determined cardiac heart muscle disorder characterized by fibro-fatty replacement of the myocardium that causes heart failure and sudden cardiac death (SCD), predominantly in young males. The disease is often caused by mutations in genes encoding proteins of the desmosomal (cell-to-cell adhesion) complex, with a significant minority caused by mutations in non-desmosomal proteins. Existing treatment options are based on SCD prevention with the implantable cardioverter defibrillator and anti-heart failure medication. Heart transplantation may also be required and there is currently no cure. Several transgenic animal models have been developed to characterize the disease, assess its progression and determine the influence of potential environmental factors. Transgenic models are also very valuable for translational therapeutic approaches, to screen new treatment options that prevent and/or regress the disease. Here we review the available ARVC animal models reported to date, highlighting the most important pathophysiological findings and discussing the effect of treatments tested so far in this setting. We also describe gaps in current disease knowledge with the goal of facilitating research and improving patient outcomes.