TY - JOUR
T1 - Role of HDACs in cardiac electropathology
T2 - Therapeutic implications for atrial fibrillation
AU - Brundel, Bianca J.J.M.
AU - Li, Jin
AU - Zhang, Deli
N1 - Copyright © 2019. Published by Elsevier B.V.
PY - 2020/3
Y1 - 2020/3
N2 - Perpetuation of atrial fibrillation (AF) is caused by electropathology, which is defined as impairment of electrical activation caused by structural and metabolic remodeling of cardiomyocytes. We previously dissected the molecular mechanisms underlying electropathology and identified an important role for histone deacetylases (HDACs). HDACs catalyze the removal of acetyl-groups from lysine residues within nucleosomal histone tails and many non-histone proteins. Various HDAC inhibitors are efficacious in attenuating electropathology, and improve contractile function in experimental AF. Emerging evidence reveals novel mechanisms by which HDAC inhibitors prevent cardiac electropathology and thereby benefit the heart during AF. These mechanisms include post-translational modification of contractile and structural proteins and changes in gene expression. In this review paper, we summarize recent findings on novel functions of zinc-dependent HDACs in electropathology and discuss the potential for pharmacological HDAC inhibition as a strategy to treat AF. This article is part of a Special Issue entitled: Cardiomyocyte biology: new pathways of differentiation and regeneration edited by Marijke Brinkm, Marcus C. Schaub, and Christian Zuppinger.
AB - Perpetuation of atrial fibrillation (AF) is caused by electropathology, which is defined as impairment of electrical activation caused by structural and metabolic remodeling of cardiomyocytes. We previously dissected the molecular mechanisms underlying electropathology and identified an important role for histone deacetylases (HDACs). HDACs catalyze the removal of acetyl-groups from lysine residues within nucleosomal histone tails and many non-histone proteins. Various HDAC inhibitors are efficacious in attenuating electropathology, and improve contractile function in experimental AF. Emerging evidence reveals novel mechanisms by which HDAC inhibitors prevent cardiac electropathology and thereby benefit the heart during AF. These mechanisms include post-translational modification of contractile and structural proteins and changes in gene expression. In this review paper, we summarize recent findings on novel functions of zinc-dependent HDACs in electropathology and discuss the potential for pharmacological HDAC inhibition as a strategy to treat AF. This article is part of a Special Issue entitled: Cardiomyocyte biology: new pathways of differentiation and regeneration edited by Marijke Brinkm, Marcus C. Schaub, and Christian Zuppinger.
KW - Atrial fibrillation
KW - Cytoskeleton
KW - Electropathology
KW - HDACs
KW - Microtubule
KW - Structural remodeling
UR - http://www.scopus.com/inward/record.url?scp=85063279732&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.bbamcr.2019.03.006
DO - https://doi.org/10.1016/j.bbamcr.2019.03.006
M3 - Review article
C2 - 30880147
SN - 0167-4889
VL - 1867
JO - Biochimica et Biophysica Acta. Molecular Cell Research
JF - Biochimica et Biophysica Acta. Molecular Cell Research
IS - 3
M1 - 118459
ER -