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Molecular mechanisms of arrhythmogenic cardiomyopathy

Nature reviews cardiology, 2019-09, Vol.16 (9), p.519-537 [Peer Reviewed Journal]

COPYRIGHT 2019 Nature Publishing Group ;Springer Nature Limited 2019. ;ISSN: 1759-5002 ;EISSN: 1759-5010 ;DOI: 10.1038/s41569-019-0200-7 ;PMID: 31028357

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Title:
Molecular mechanisms of arrhythmogenic cardiomyopathy
Author: Austin, Karyn M ; Trembley, Michael A ; Chandler, Stephanie F ; Sanders, Stephen P ; Saffitz, Jeffrey E ; Abrams, Dominic J ; Pu, William T
Subjects: Adaptor Proteins, Signal Transducing - metabolism ; Adipogenesis - genetics ; Analysis ; Animals ; Apoptosis ; Arrhythmias, Cardiac - genetics ; Arrhythmias, Cardiac - metabolism ; Arrhythmias, Cardiac - pathology ; Cardiac arrhythmia ; Cardiomyopathies - genetics ; Cardiomyopathies - metabolism ; Cardiomyopathies - pathology ; Cardiomyopathy ; Care and treatment ; Cell Line ; Diagnosis ; Disease Models, Animal ; Fibrosis ; Genetic disorders ; Heart diseases ; Heart failure ; Hippo Signaling Pathway ; Humans ; Inflammation - metabolism ; MicroRNAs - metabolism ; Molecular mechanics ; Mutation ; Myocytes, Cardiac - pathology ; Myocytes, Cardiac - physiology ; Pathogenesis ; Prevention ; Protein Serine-Threonine Kinases - metabolism ; Risk factors ; Transcription Factors - metabolism ; Wnt Signaling Pathway ; YAP-Signaling Proteins
Is Part Of: Nature reviews cardiology, 2019-09, Vol.16 (9), p.519-537
Description: Arrhythmogenic cardiomyopathy is a genetic disorder characterized by the risk of life-threatening arrhythmias, myocardial dysfunction and fibrofatty replacement of myocardial tissue. Mutations in genes that encode components of desmosomes, the adhesive junctions that connect cardiomyocytes, are the predominant cause of arrhythmogenic cardiomyopathy and can be identified in about half of patients with the condition. However, the molecular mechanisms leading to myocardial destruction, remodelling and arrhythmic predisposition remain poorly understood. Through the development of animal, induced pluripotent stem cell and other models of disease, advances in our understanding of the pathogenic mechanisms of arrhythmogenic cardiomyopathy over the past decade have brought several signalling pathways into focus. These pathways include canonical and non-canonical WNT signalling, the Hippo-Yes-associated protein (YAP) pathway and transforming growth factor-β signalling. These studies have begun to identify potential therapeutic targets whose modulation has shown promise in preclinical models. In this Review, we summarize and discuss the reported molecular mechanisms underlying the pathogenesis of arrhythmogenic cardiomyopathy.
Publisher: England: Nature Publishing Group
Language: English
Identifier: ISSN: 1759-5002
EISSN: 1759-5010
DOI: 10.1038/s41569-019-0200-7
PMID: 31028357
Source: MEDLINE
ProQuest Central

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Molecular mechanisms of arrhythmogenic cardiomyopathy

COPYRIGHT 2019 Nature Publishing Group ;Springer Nature Limited 2019. ;ISSN: 1759-5002 ;EISSN: 1759-5010 ;DOI: 10.1038/s41569-019-0200-7 ;PMID: 31028357

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