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Entry
map05412                    Pathway                                

Name
Arrhythmogenic right ventricular cardiomyopathy (ARVC)
Description
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited heart muscle disease that may result in arrhythmia, heart failure, and sudden death. The hallmark pathological findings are progressive myocyte loss and fibrofatty replacement, with a predilection for the right ventricle. A number of genetic studies have identified mutations in various components of the cardiac desmosome that have important roles in the pathogenesis of ARVC. Disruption of desmosomal function by defective proteins might lead to death of myocytes under mechanical stress. The myocardial injury may be accompanied by inflammation. Since regeneration of cardiac myocytes is limited, repair by fibrofatty replacement occurs. Several studies have implicated that desmosome dysfunction results in the delocalization and nuclear translocation of plakoglobin. As a result, competition between plakoglobin and beta-catenin will lead to the inhibition of Wnt/beta-catenin signaling, resulting in a shift from a myocyte fate towards an adipocyte fate of cells. The ryanodine receptor plays a crucial part in electromechanical coupling by control of release of calcium from the sarcoplasmic reticulum into the cytosol. Therefore, defects in this receptor could result in an imbalance of calcium homeostasis that might trigger cell death.
Class
Human Diseases; Cardiovascular diseases
BRITE hierarchy
Pathway map
map05412  Arrhythmogenic right ventricular cardiomyopathy (ARVC)
map05412

Ortholog table
Disease
H00293  Arrhythmogenic right ventricular cardiomyopathy
H00669  Naxos disease
H00728  Brugada syndrome
Reference
  Authors
Herren T, Gerber PA, Duru F
  Title
Arrhythmogenic right ventricular cardiomyopathy/dysplasia: a not so rare "disease of the desmosome" with multiple clinical presentations.
  Journal
Clin Res Cardiol 98:141-58 (2009)
DOI:10.1007/s00392-009-0751-4
Reference
  Authors
van Tintelen JP, Hofstra RM, Wiesfeld AC, van den Berg MP, Hauer RN, Jongbloed JD
  Title
Molecular genetics of arrhythmogenic right ventricular cardiomyopathy: emerging horizon?
  Journal
Curr Opin Cardiol 22:185-92 (2007)
DOI:10.1097/HCO.0b013e3280d942c4
Reference
  Authors
Fatkin D, Graham RM
  Title
Molecular mechanisms of inherited cardiomyopathies.
  Journal
Physiol Rev 82:945-80 (2002)
DOI:10.1152/physrev.00012.2002
Reference
  Authors
Franz WM, Muller OJ, Katus HA
  Title
Cardiomyopathies: from genetics to the prospect of treatment.
  Journal
Lancet 358:1627-37 (2001)
DOI:10.1016/S0140-6736(01)06657-0
Reference
  Authors
MacRae CA, Birchmeier W, Thierfelder L
  Title
Arrhythmogenic right ventricular cardiomyopathy: moving toward mechanism.
  Journal
J Clin Invest 116:1825-8 (2006)
DOI:10.1172/JCI29174
Reference
  Authors
Awad MM, Calkins H, Judge DP
  Title
Mechanisms of disease: molecular genetics of arrhythmogenic right ventricular dysplasia/cardiomyopathy.
  Journal
Nat Clin Pract Cardiovasc Med 5:258-67 (2008)
DOI:10.1038/ncpcardio1182
Reference
  Authors
Sen-Chowdhry S, Syrris P, McKenna WJ
  Title
Genetics of right ventricular cardiomyopathy.
  Journal
J Cardiovasc Electrophysiol 16:927-35 (2005)
DOI:10.1111/j.1540-8167.2005.40842.x
Reference
  Authors
Ahmad F, Seidman JG, Seidman CE
  Title
The genetic basis for cardiac remodeling.
  Journal
Annu Rev Genomics Hum Genet 6:185-216 (2005)
DOI:10.1146/annurev.genom.6.080604.162132
KO pathway
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