Abstract
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a heart muscle disorder characterized by fibro-fatty replacement of cardiomyocytes. The cardinal manifestations are arrhythmias, sudden cardiac death, and seldom heart failure. Mutations in genes encoding desmosomal proteins and their interaction partners have been implicated in the pathogenesis of ARVC and it is now widely accepted that ARVC is a disease caused by abnormal cell–cell adhesion. The mechanism(s) by which mutations in desmosomal proteins lead to fibro-fatty replacement remains to be fully elucidated. To this aim over the last 10 years different transgenic and targeted mouse models have been developed, these models and what they have taught us will be discussed in this review.
Highlights
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an important cause of ventricular arrhythmias and sudden cardiac death, especially in the young and in athletes (Marcus et al, 1982; Thiene et al, 1988; Basso et al, 2009)
Over the years several mouse models have been developed to investigate the mechanisms of disease development in ARVC (Pilichou et al, 2011), focusing on four of the desmosomal proteins: Plakophilin-2, Plakoglobin (γ-catenin), Desmoplakin, and Desmoglein 2
None of the models show the clear fatty infiltrations seen in human, this is most likely a reflection of the different composition of the extracellular matrix and non-cardiomyocytes interstitial cells in the wild type murine heart, which lacks a significant adipocyte population (Pilichou et al, 2009)
Summary
Reviewed by: Sebastian Pieperhoff, University of Edinburgh, Scotland Weinian Shou, Indiana University, USA. Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a heart muscle disorder characterized by fibro-fatty replacement of cardiomyocytes. The cardinal manifestations are arrhythmias, sudden cardiac death, and seldom heart failure. Mutations in genes encoding desmosomal proteins and their interaction partners have been implicated in the pathogenesis of ARVC and it is widely accepted that ARVC is a disease caused by abnormal cell–cell adhesion. The mechanism(s) by which mutations in desmosomal proteins lead to fibro-fatty replacement remains to be fully elucidated. To this aim over the last 10 years different transgenic and targeted mouse models have been developed, these models and what they have taught us will be discussed in this review
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