TY - JOUR
T1 - Cytoskeletal Protein Variants Driving Atrial Fibrillation
T2 - Potential Mechanisms of Action
AU - van Wijk, Stan W.
AU - Su, Wei
AU - Wijdeveld, Leonoor F. J. M.
AU - Ramos, Kennedy S.
AU - Brundel, Bianca J. J. M.
N1 - Funding Information: This research was funded by DHF, DZKH (DnAFix project, 2020B003, 2020) and the Atrial Fibrillation Innovation Platform (www.AFIPonline.org, accessed on 9 December 2021). Publisher Copyright: © 2022 by the authors.
PY - 2022/2/1
Y1 - 2022/2/1
N2 - 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.
AB - 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.
KW - Atrial fibrillation
KW - Cardiomyocytes
KW - Cytoskeletal proteins
KW - DNA damage
KW - Genetics
UR - http://www.scopus.com/inward/record.url?scp=85123718506&partnerID=8YFLogxK
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85123718506&origin=inward
U2 - https://doi.org/10.3390/cells11030416
DO - https://doi.org/10.3390/cells11030416
M3 - Article
C2 - 35159226
SN - 2073-4409
VL - 11
JO - Cells
JF - Cells
IS - 3
M1 - 416
ER -