Cytoskeletal Protein Variants Driving Atrial Fibrillation: Potential Mechanisms of Action

Cells

Leonoor F. J. M. Wijdeveld¹  Wei Su¹  Stan W. van Wijk¹  Bianca J. J. M. Brundel¹  Kennedy S. Ramos¹ 

[1] Department of Physiology, Amsterdam Cardiovascular Sciences, Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands;

关键词: atrial fibrillation;    genetics;    cytoskeletal proteins;    cardiomyocytes;    DNA damage;   

DOI  :  10.3390/cells11030416

来源: DOAJ

【 摘 要 】

The most common clinical tachyarrhythmia, atrial fibrillation (AF), is present in 1–2% of the population. Although common risk factors, including hypertension, diabetes, and obesity, frequently underlie AF onset, it has been recognized that in 15% of the AF population, AF is familial. In these families, genome and exome sequencing techniques identified variants in the non-coding genome (i.e., variant regulatory elements), genes encoding ion channels, as well as genes encoding cytoskeletal (-associated) proteins. Cytoskeletal protein variants include variants in desmin, lamin A/C, titin, myosin heavy and light chain, junctophilin, nucleoporin, nesprin, and filamin C. These cytoskeletal protein variants have a strong association with the development of cardiomyopathy. Interestingly, AF onset is often represented as the initial manifestation of cardiac disease, sometimes even preceding cardiomyopathy by several years. Although emerging research findings reveal cytoskeletal protein variants to disrupt the cardiomyocyte structure and trigger DNA damage, exploration of the pathophysiological mechanisms of genetic AF is still in its infancy. In this review, we provide an overview of cytoskeletal (-associated) gene variants that relate to genetic AF and highlight potential pathophysiological pathways that drive this arrhythmia.

【 授权许可】

Unknown