Abstract
Arrhythmogenic cardiomyopathy (ACM) is a primary myocardial disease. It is characterized
by frequent ventricular arrhythmias and increased risk of sudden cardiac death typically
arising as an early manifestation before the onset of significant myocardial remodelling.
Myocardial degeneration, often confined to the right ventricular free wall, with replacement
by fibrofatty scar tissue, develops in many patients. ACM is a familial disease but
genetic penetrance can be low and disease expression is highly variable. Inflammation
might promote disease progression. It also appears that exercise increases disease
penetrance and accelerates its development. More than 60% of probands harbour mutations
in genes that encode desmosomal proteins, which has raised the possibility that defective
cell-cell adhesion might play a role in disease pathogenesis. Recent advances have
implicated changes in the canonical wingless-type mouse mammary tumour virus integration
site (Wnt)/β-catenin and Hippo signalling pathways and defects in forwarding trafficking
of ion channels and other proteins to the intercalated disk in cardiac myocytes. In
this review we summarize the current understanding of the pathogenesis of ACM and
highlight future research directions.
Résumé
La cardiomyopathie arythmogène (CMA) est une maladie myocardique primitive. Elle est
caractérisée par de fréquentes arythmies ventriculaires et l’augmentation du risque
de mort cardiaque subite se manifestant typiquement de manière précoce avant l’apparition
d’un remodelage myocardique significatif. La dégénération myocardique, souvent limitée
à la paroi libre du ventricule droit, avec le remplacement du tissu cicatriciel fibro-adipeux,
se développe chez plusieurs patients. La MCA est une maladie familiale, mais la pénétrance
peut être faible et l’expressivité de la maladie est très variable. L’inflammation
favoriserait la progression de la maladie. Il semble également que l’exercice augmente
la pénétrance de la maladie et accélère son développement. Plus de 60 % des proposants
portent des mutations dans les gènes qui encodent les protéines desmosomales, ce qui
soulève la possibilité que l’adhérence cellule-cellule défectueuse puisse jouer un
rôle dans la pathogenèse de la maladie. De récentes avancées ont impliqué des changements
dans les voies de signalisation Wnt/ β-caténine (voie canonique) et Hippo et des anomalies
en transférant le trafic des canaux ioniques et les autres protéines au disque intercalé
dans les myocytes cardiaques. Dans cette revue, nous résumons les connaissances actuelles
sur la pathogenèse de la MCA et dégageons les orientations futures de la recherche.
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Article info
Publication history
Published online: April 23, 2015
Accepted:
April 13,
2015
Received:
March 27,
2015
Footnotes
See page 1322 for disclosure information.
Identification
Copyright
© 2015 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.
