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- W2093957264 abstract "Background— Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited disorder that causes sudden death and right ventricular heart failure in the young. Clinical data suggest that competitive sports may provoke ARVC in susceptible persons. Genetically, loss-of-function mutations in desmosomal proteins (plakophilin, desmoplakin, or plakoglobin) have been associated with ARVC. To test the hypothesis that reduced desmosomal protein expression causes ARVC, we studied the cardiac effects of heterozygous plakoglobin deficiency in mice. Methods and Results— Ten-month-old heterozygous plakoglobin-deficient mice (plakoglobin +/− ) had increased right ventricular volume, reduced right ventricular function, and spontaneous ventricular ectopy (all P <0.05). Left ventricular size and function were not altered. Isolated, perfused plakoglobin +/− hearts had spontaneous ventricular tachycardia of right ventricular origin and prolonged right ventricular conduction times compared with wild-type hearts. Endurance training accelerated the development of right ventricular dysfunction and arrhythmias in plakoglobin +/− mice. Histology and electron microscopy did not identify right ventricular abnormalities in affected animals. Conclusions— Heterozygous plakoglobin deficiency provokes ARVC. Manifestation of the phenotype is accelerated by endurance training. This suggests a functional role for plakoglobin and training in the development of ARVC." @default.
- W2093957264 created "2016-06-24" @default.
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- W2093957264 date "2006-10-24" @default.
- W2093957264 modified "2023-10-18" @default.
- W2093957264 title "Age- and Training-Dependent Development of Arrhythmogenic Right Ventricular Cardiomyopathy in Heterozygous Plakoglobin-Deficient Mice" @default.
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- W2093957264 doi "https://doi.org/10.1161/circulationaha.106.624502" @default.
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