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Arrhythmogenic Right Ventricular Cardiomyopathy
  1. Jeffrey E. Saffitz, MD, PhD*,
  2. Angeliki Asimaki, PhD*,
  3. Hayden Huang, PhD
  1. From the *Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA; and †Department of Biomedical Engineering, Columbia University, New York, NY.
  1. Received September 9, 2009, and in revised form October 6, 2009.
  2. Accepted for publication October 6, 2009.
  3. Reprints: Jeffrey E. Saffitz, MD, PhD, Department of Pathology, Beth Israel Deaconess Medical Center, 330 Brookline Ave, Boston, MA 02115. E-mail: jsaffitz{at}bidmc.harvard.edu.
  4. Supported by the Kenneth M. Rosen Fellowship in Cardiac Pacing and Electrophysiology from the Heart Rhythm Society (A. A.) and by the Lerner Fund (H. H.), and the symposium was supported in part by a grant from the National Center for Research Resources (R13 RR023236).

New Insights Into Disease Mechanisms and Diagnosis

Abstract

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a primary heart muscle disorder characterized by the early occurrence of serious tachyarrhythmias often out of proportion to the extent of structural changes and contractile derangement. Approximately 40% of patients with ARVC have one or more mutations in genes encoding proteins in desmosomes, intercellular adhesion junctions which, in cardiac myocytes, reside within intercalated disks. Some desmosomal proteins fulfill roles both as structural proteins in cell-cell adhesion junctions and as nuclear signaling molecules. It has been proposed that mutations in desmosomal proteins implicated in ARVC may perturb the normal balance of protein in junctions and the cytosol which, in turn, could promote dysregulated gene expression circumventing the normal controls of Wnt signaling pathways. This review highlights recent advances in understanding the pathogenesis of ARVC and presents evidence, suggesting that the disease is caused by a combination of altered cellular biomechanical behavior and altered signaling.

Key Words
  • desmosome
  • plakoglobin
  • gap junctions
  • arrhythmias
  • biomechanical behavior

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