Healthy and Unhealthy Cardiac Progenitor Cells Modify the Pathogenesis of Myocardial Diseases
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Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is a life-threatening inherited cardiomyopathy with an estimated prevalence of 1 per 5000 individuals characterized by the replacement of the cardiac myocytes with fibrofatty tissue leading to ventricular arrhythmias, right ventricular failure, and sudden cardiac death.1 ARVD/C is commonly inherited in an autosomal dominant manner with an incomplete penetrance and variable expressivity caused by mutations in desmosomal genes (eg, plakoglobin, plakophilin-2, desmoplakin, desmoglein-2, and desmocollin-2) and several nondesmosomal genes (such as ryanodine receptor, phospholamban, transmembrane protein 43, titin, and TGFβ3).1
Article, see p 41
Mature cardiac myocytes express desmosomal proteins. However, differentiated cardiac myocytes are unlikely to transdifferentiate into fibro-adipocytes. Interestingly, some types of stem and progenitor cells are able to express desmosomal proteins and hence might contribute to the formation of fibrofatty tissue in ARVD/C.2 Joe et al3 described a population of fibro-adipogenic progenitors (FAPs) in the skeletal muscle that express platelet-derived growth factor receptor-α (PDGFRA). FAPs are present in healthy muscular tissue. They rapidly enter the cell cycle in response to acute muscle injury but do not generate myofibers. FAP along with the satellite cells participate in muscle regeneration providing a source of cytokines that regulate satellite cell activity and establishing an environment enhancing myogenic differentiation.4 However, under pathological conditions, FAPs may impair muscle structure and function. Uezumi et al5 demonstrated a participation …