Arrhythmogenic Right Ventricular Cardiomyopathy Pathway - CISMeF
Arrhythmogenic Right Ventricular Cardiomyopathy PathwayNCIt concept
Preferred Label : Arrhythmogenic Right Ventricular Cardiomyopathy Pathway;
NCIt synonyms : ARVC Pathway;
NCIt related terms : Arrhythmogenic right ventricular cardiomyopathy (ARVC);
Alternative definition : KEGG: 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 ARVD/C. 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.;