Animal models of arrhythmogenic right ventricular cardiomyopathy: what have we learned and where do we go? Insight for therapeutics

Basic Res Cardiol. 2017 Sep;112(5):50. doi: 10.1007/s00395-017-0640-3. Epub 2017 Jul 7.

Abstract

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a rare genetically-determined cardiac heart muscle disorder characterized by fibro-fatty replacement of the myocardium that results in 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 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, antiarrhythmic drugs, and anti-heart failure medication. Heart transplantation may also be required and there is currently no cure. Several genetically modified animal models have been developed to characterize the disease, assess its progression, and determine the influence of potential environmental factors. These models have also been very valuable for translational therapeutic approaches, to screen new treatment options that prevent and/or reverse 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 our knowledge of the disease, with the goal of stimulating research and improving patient outcomes.

Keywords: ARVC; Animal models; Desmosomes; Exercise; Therapies.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Arrhythmia Agents / adverse effects
  • Anti-Arrhythmia Agents / therapeutic use*
  • Arrhythmogenic Right Ventricular Dysplasia / genetics
  • Arrhythmogenic Right Ventricular Dysplasia / metabolism
  • Arrhythmogenic Right Ventricular Dysplasia / physiopathology
  • Arrhythmogenic Right Ventricular Dysplasia / therapy*
  • Cardiotonic Agents / adverse effects
  • Cardiotonic Agents / therapeutic use*
  • Defibrillators, Implantable
  • Disease Models, Animal
  • Electric Countershock* / adverse effects
  • Electric Countershock* / instrumentation
  • Genetic Predisposition to Disease
  • Humans
  • Mutation
  • Myocardium / metabolism
  • Myocardium / pathology
  • Phenotype
  • Physical Exertion

Substances

  • Anti-Arrhythmia Agents
  • Cardiotonic Agents