The pathobiology of arrhythmogenic cardiomyopathy

Abstract

This review highlights current knowledge about arrhythmogenic cardiomyopathy and considers clinical, pathological, genetic, biomechanical, and pathophysiological aspects of disease pathogenesis. Although relatively uncommon, arrhythmogenic cardiomyopathy is of particular interest as a model system for study. It is caused in at least half of all cases by single-gene mutations that provide direct entry points into studies designed to elucidate mechanisms of disease. These mutations involve proteins that form desmosomes, directly implicating altered cellular biomechanical properties in disease pathogenesis and providing opportunities to investigate more broadly the ways in which abnormal cell and tissue biomechanics induce cardiac myocyte injury and alter cell biology. The highly arrhythmogenic phenotype is a cardinal feature of the disease. A more complete understanding of the pathogenesis of this aspect of arrhythmogenic cardiomyopathy may shed light onto the basic mechanisms underlying lethal ventricular arrhythmias and sudden cardiac death in more common forms of heart disease.