title: Targeting cardiac fibroblasts to treat fibrosis of the heart: focus on HDACs.
abstract: Cardiac fibrosis is implicated in numerous physiologic and pathologic conditions, including scar formation, heart failure and cardiac arrhythmias. However the specific cells and signaling pathways mediating this process are poorly understood. Lysine acetylation of nucleosomal histone tails is an important mechanism for the regulation of gene expression. Additionally, proteomic studies have revealed that thousands of proteins in all cellular compartments are subject to reversible lysine acetylation, and thus it is becoming clear that this post-translational modification will rival phosphorylation in terms of biological import. Acetyl groups are conjugated to lysine by histone acetyltransferases (HATs) and removed from lysine by histone deacetylases (HDACs). Recent studies have shown that pharmacologic agents that alter lysine acetylation by targeting HDACs have the remarkable ability to block pathological fibrosis. Here, we review the current understanding of cardiac fibroblasts and the fibrogenic process with respect to the roles of lysine acetylation in the control of disease-related cardiac fibrosis. Potential for small molecule HDAC inhibitors as anti-fibrotic therapeutics that target cardiac fibroblasts is highlighted. This article is part of a Special Issue entitled "Myocyte-Fibroblast Signalling in Myocardium."
authors.affiliation: Department of Medicine, Division of Cardiology, University of Colorado Denver, 12700 E. 19th Ave., Aurora, CO 80045-0508, USA.
authors.forename: Katherine B
authors.initials: KB
authors.lastname: Schuetze
authors.affiliation: Department of Medicine, Division of Cardiology, University of Colorado Denver, 12700 E. 19th Ave., Aurora, CO 80045-0508, USA. Electronic address: timothy.mckinsey@ucdenver.edu.
authors.forename: Timothy A
authors.initials: TA
authors.lastname: McKinsey
authors.affiliation: Department of Medicine, Division of Cardiology, University of Colorado Denver, 12700 E. 19th Ave., Aurora, CO 80045-0508, USA. Electronic address: Carlin.long@dhha.org.
authors.forename: Carlin S
authors.initials: CS
authors.lastname: Long
mesh_terms: D000107:Acetylation; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D005355:Fibrosis / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D005786:Gene Expression Regulation; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008239:Lysine / Q000378:metabolism; D058990:Molecular Targeted Therapy; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D058628:Myofibroblasts / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D011499:Protein Processing, Post-Translational; D015398:Signal Transduction
chemical_list: D056572:Histone Deacetylase Inhibitors; D006657:Histones; D006655:Histone Deacetylases; D008239:Lysine
keywords: Epigenetics; Fibroblast; Fibrosis; Histone acetylation