Arrhythmogenic right ventricular cardiomyopathy: moving toward mechanism.
Mutations in genes encoding desmosomal proteins have been identified as the major cause of arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVC), in which the right ventricle is "replaced" by fibrofatty tissue, resulting in lethal arrhythmias. In this issue of the JCI, Garcia-Gras et al. demonstrate that cardiac-specific loss of the desmosomal protein desmoplakin is sufficient to cause nuclear translocation of plakoglobin, upregulation of adipogenic genes in vitro, and a shift from a cardiomyocyte to an adipocyte cell fate in vivo (see the related article beginning on page 2012). This evidence for potential Wnt/beta-catenin signaling defects sets the scene for a comprehensive exploration of the contributions of this pathway to the pathophysiology of ARVC, not only through perturbation of cardiac patterning and development, but also through effects on myocardial differentiation and physiology.
MacRae
Calum A
CA
Cardiovascular Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Birchmeier
Walter
W
Thierfelder
Ludwig
L
D000818:Animals; D019571:Arrhythmogenic Right Ventricular Dysplasia / Q000235:genetics / Q000378:metabolism*; D051180:Desmoplakins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D051191:Plakophilins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D051153:Wnt Proteins / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism; D051185:gamma Catenin / Q000378:metabolism*
D051180:Desmoplakins; D051191:Plakophilins; D051153:Wnt Proteins; D051176:beta Catenin; D051185:gamma Catenin