Calcium as a Key Player in Arrhythmogenic Cardiomyopathy: Adhesion Disorder or Intracellular Alteration?
AbstractArrhythmogenic cardiomyopathy (ACM) is an inherited heart disease characterized by sudden death in young people and featured by fibro-adipose myocardium replacement, malignant arrhythmias, and heart failure. To date, no etiological therapies are available. Mutations in desmosomal genes cause abnormal mechanical coupling, trigger pro-apoptotic signaling pathways, and induce fibro-adipose replacement. Here, we discuss the hypothesis that the ACM causative mechanism involves a defect in the expression and/or activity of the cardiac Ca2+ handling machinery, focusing on the available data supporting this hypothesis. The Ca2+ toolkit is heavily remodeled in cardiomyocytes derived from a mouse model of ACM defective of the desmosomal protein plakophilin-2. Furthermore, ACM-related mutations were found in genes encoding for proteins involved in excitation‒contraction coupling, e.g., type 2 ryanodine receptor and phospholamban. As a consequence, the sarcoplasmic reticulum becomes more eager to release Ca2+, thereby inducing delayed afterdepolarizations and impairing cardiac contractility. These data are supported by preliminary observations from patient induced pluripotent stem-cell-derived cardiomyocytes. Assessing the involvement of Ca2+ signaling in the pathogenesis of ACM could be beneficial in the treatment of this life-threatening disease. View Full-Text
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Moccia, F.; Lodola, F.; Stadiotti, I.; Pilato, C.A.; Bellin, M.; Carugo, S.; Pompilio, G.; Sommariva, E.; Maione, A.S. Calcium as a Key Player in Arrhythmogenic Cardiomyopathy: Adhesion Disorder or Intracellular Alteration? Int. J. Mol. Sci. 2019, 20, 3986.
Moccia F, Lodola F, Stadiotti I, Pilato CA, Bellin M, Carugo S, Pompilio G, Sommariva E, Maione AS. Calcium as a Key Player in Arrhythmogenic Cardiomyopathy: Adhesion Disorder or Intracellular Alteration? International Journal of Molecular Sciences. 2019; 20(16):3986.Chicago/Turabian Style
Moccia, Francesco; Lodola, Francesco; Stadiotti, Ilaria; Pilato, Chiara A.; Bellin, Milena; Carugo, Stefano; Pompilio, Giulio; Sommariva, Elena; Maione, Angela S. 2019. "Calcium as a Key Player in Arrhythmogenic Cardiomyopathy: Adhesion Disorder or Intracellular Alteration?" Int. J. Mol. Sci. 20, no. 16: 3986.
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