Potential new mechanisms of pro-arrhythmia in arrhythmogenic cardiomyopathy: focus on calcium sensitive pathways

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• 作者：C. J. M. van Opbergen ; M. Delmar ; T. A. B. van Veen
• 关键词：Arrhythmogenic cardiomyopathy ; Calcium ; Arrhythmia ; CaMKII ; Phospholamban
• 刊名：Netherlands Heart Journal
• 出版年：2017
• 出版时间：March 2017
• 年：2017
• 卷：25
• 期：3
• 页码：157-169
• 全文大小：1016KB
• 刊物主题：Cardiology; Medical Education;
• 出版者：Bohn Stafleu van Loghum
• ISSN：1876-6250
• 卷排序：25

文摘

Arrhythmogenic cardiomyopathy, or its most well-known subform arrhythmogenic right ventricular cardiomyopathy (ARVC), is a cardiac disease mainly characterised by a gradual replacement of the myocardial mass by fibrous and fatty tissue, leading to dilatation of the ventricular wall, arrhythmias and progression towards heart failure. ARVC is commonly regarded as a disease of the intercalated disk in which mutations in desmosomal proteins are an important causative factor. Interestingly, the Dutch founder mutation PLN R14Del has been identified to play an additional, and major, role in ARVC patients within the Netherlands. This is remarkable since the phospholamban (PLN) protein plays a leading role in regulation of the sarcoplasmic reticulum calcium load rather than in the establishment of intercellular integrity. In this review we outline the intracellular cardiac calcium dynamics and relate pathophysiological signalling, induced by disturbed calcium handling, with activation of calmodulin dependent kinase II (CaMKII) and calcineurin A (CnA). We postulate a thus far unrecognised role for Ca2+ sensitive signalling proteins in maladaptive remodelling of the macromolecular protein complex that forms the intercalated disk, during pro-arrhythmic remodelling of the heart.