Role of HDACs in cardiac electropathology: Therapeutic implications for atrial fibrillation

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Abstract

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.

Original languageEnglish
JournalBiochimica et Biophysica Acta. Molecular Cell Research
DOIs
Publication statusE-pub ahead of print - 1 Jan 2019

Cite this

@article{b17b4c41596f418493c1fe6a5ef670c6,
title = "Role of HDACs in cardiac electropathology: Therapeutic implications for atrial fibrillation",
abstract = "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.",
keywords = "Atrial fibrillation, Cytoskeleton, Electropathology, HDACs, Microtubule, Structural remodeling",
author = "Brundel, {Bianca J.J.M.} and Jin Li and Deli Zhang",
note = "Copyright {\circledC} 2019. Published by Elsevier B.V.",
year = "2019",
month = "1",
day = "1",
doi = "10.1016/j.bbamcr.2019.03.006",
language = "English",
journal = "Biochimica et Biophysica Acta. Molecular Cell Research",
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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 - 2019/1/1

Y1 - 2019/1/1

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

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U2 - 10.1016/j.bbamcr.2019.03.006

DO - 10.1016/j.bbamcr.2019.03.006

M3 - Review article

JO - Biochimica et Biophysica Acta. Molecular Cell Research

JF - Biochimica et Biophysica Acta. Molecular Cell Research

SN - 0167-4889

ER -