Molecular genetics and pathogenesis of arrhythmogenic right ventricular cardiomyopathy: a disease of cardiac stem cells
- PMID: 21267716
- DOI: 10.1007/s00246-011-9890-2
Molecular genetics and pathogenesis of arrhythmogenic right ventricular cardiomyopathy: a disease of cardiac stem cells
Abstract
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 β3, 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.
Similar articles
-
Arrhythmogenic right ventricular cardiomyopathy is a disease of cardiac stem cells.Curr Opin Cardiol. 2010 May;25(3):222-8. doi: 10.1097/HCO.0b013e3283376daf. Curr Opin Cardiol. 2010. PMID: 20124997 Free PMC article.
-
Genetic fate mapping identifies second heart field progenitor cells as a source of adipocytes in arrhythmogenic right ventricular cardiomyopathy.Circ Res. 2009 May 8;104(9):1076-84. doi: 10.1161/CIRCRESAHA.109.196899. Epub 2009 Apr 9. Circ Res. 2009. PMID: 19359597 Free PMC article.
-
Mutations in desmoglein-2 gene are associated with arrhythmogenic right ventricular cardiomyopathy.Circulation. 2006 Mar 7;113(9):1171-9. doi: 10.1161/CIRCULATIONAHA.105.583674. Epub 2006 Feb 27. Circulation. 2006. PMID: 16505173
-
Arrhythmogenic Right Ventricular Cardiomyopathy Overview.2005 Apr 18 [updated 2023 May 11]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2025. 2005 Apr 18 [updated 2023 May 11]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2025. PMID: 20301310 Free Books & Documents. Review.
-
Mutations with pathogenic potential in proteins located in or at the composite junctions of the intercalated disk connecting mammalian cardiomyocytes: a reference thesaurus for arrhythmogenic cardiomyopathies and for Naxos and Carvajal diseases.Cell Tissue Res. 2012 May;348(2):325-33. doi: 10.1007/s00441-012-1365-0. Epub 2012 Mar 27. Cell Tissue Res. 2012. PMID: 22450909 Free PMC article. Review.
Cited by
-
The hippo pathway is activated and is a causal mechanism for adipogenesis in arrhythmogenic cardiomyopathy.Circ Res. 2014 Jan 31;114(3):454-68. doi: 10.1161/CIRCRESAHA.114.302810. Epub 2013 Nov 25. Circ Res. 2014. PMID: 24276085 Free PMC article.
-
Effects of CMYA1 overexpression on cardiac structure and function in mice.Acta Biochim Biophys Sin (Shanghai). 2021 Apr 15;53(5):593-600. doi: 10.1093/abbs/gmab029. Acta Biochim Biophys Sin (Shanghai). 2021. PMID: 33792654 Free PMC article.
-
Nuclear plakoglobin is essential for differentiation of cardiac progenitor cells to adipocytes in arrhythmogenic right ventricular cardiomyopathy.Circ Res. 2011 Dec 9;109(12):1342-53. doi: 10.1161/CIRCRESAHA.111.255075. Epub 2011 Oct 20. Circ Res. 2011. PMID: 22021931 Free PMC article.
-
New insights into the roles of Xin repeat-containing proteins in cardiac development, function, and disease.Int Rev Cell Mol Biol. 2014;310:89-128. doi: 10.1016/B978-0-12-800180-6.00003-7. Int Rev Cell Mol Biol. 2014. PMID: 24725425 Free PMC article. Review.
-
Essential role of the zinc finger transcription factor Casz1 for mammalian cardiac morphogenesis and development.J Biol Chem. 2014 Oct 24;289(43):29801-16. doi: 10.1074/jbc.M114.570416. Epub 2014 Sep 4. J Biol Chem. 2014. PMID: 25190801 Free PMC article.
References
MeSH terms
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Miscellaneous