Molecular Genetics and Pathogenesis of Arrhythmogenic Right Ventricular Cardiomyopathy: A Disease of Cardiac Stem Cells
- نوع فایل : کتاب
- زبان : انگلیسی
- مؤلف : Raffaella Lombardi • A. J. Marian
- چاپ و سال / کشور: 2011
Description
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an uncommon cardiomyopathy characterized by fibroadiposis replacing cardiac myocytes, predominantly in the right ventricle. The clinical phenotype is characterized by cardiac arrhythmias, sudden cardiac death, and heart failure. The molecular genetic basis of ARVC is partially known. Mutations in DSP (desmoplakin), JUP (plakoglobin), PKP2 (plakophilin 2), DSG2 (desmoglein 2), and DSC2 (desmocollin 2) are responsible for approximately half of the cases. Mutations in TMEM43 and TGFB3, encoding transmembrane protein 43 and transforming growth factor b3, respectively, also have been associated with ARVC. The molecular pathogenesis of ARVC has at least two components. The first component is fibroadiposis, which is the characteristics hallmark of the disease. The second is cardiac dysfunction, which is primarily due to impaired myocyte-to-myocyte attachment. The pathogenesis of fibroadiposis involves partial nuclear translocation of plakoglobin (PG) and subsequent suppression of canonical Wnt signaling, which is involved in the development of the right ventricle and its outflow tract, the predominant sites of involvement in ARVC. Suppression of the canonical Wnt signaling results in a switch to adipogenesis in the second heart field progenitor cells. Accordingly, ARVC is a disease of cardiac progenitor cells that have gone awry and differentiated to adipocytes.
Pediatr Cardiol (2011) 32:360–365 DOI 10.1007/s00246-011-9890-2 Received: 30 December 2010 / Accepted: 10 January 2011 / Published online: 26 January 2011
