Arrhythmogenic right ventricular cardiomyopathy: moving toward mechanism
J. Clin. Invest. Calum A. MacRae, et al. 116:1825 doi:10.1172/JCI29174 [Go to this article.]

Figure 1
Cardiac-specific restriction of the desmosomal protein desmoplakin causes nuclear localization of plakoglobin and reduced Wnt/β-catenin signaling, recapitulating human ARVC. (A) ARVC predominantly affects the right ventricle of the heart. (B) The intercalated discs of cardiac myocytes are characterized by gap junctions, adherens junctions, and desmosomes. (C) Cell-cell adhesion is largely dependent on interaction of intracellular components of the desmosomal plaque such as desmoplakin and plakoglobin. (D) In this issue of the JCI, Garcia-Gras et al. (16) report that heterozygous cardiac desmoplakin-deficient mice show nuclear localization of plakoglobin and reduced Wnt/β-catenin signaling. This causes increased expression of adipogenic and fibrogenic genes in vitro, abnormal cardiac adipose tissue and fibrosis in vivo, and ventricular arrhythmias similar to human ARVC. Interactions between signaling defects and mechanical stresses are likely to be involved in the genesis of the final phenotype.