title: Acetyl-lysine erasers and readers in the control of pulmonary hypertension and right ventricular hypertrophy.
abstract: Acetylation of lysine residues within nucleosomal histone tails provides a crucial mechanism for epigenetic control of gene expression. Acetyl groups are coupled to lysine residues by histone acetyltransferases (HATs) and removed by histone deacetylases (HDACs), which are also commonly referred to as "writers" and "erasers", respectively. In addition to altering the electrostatic properties of histones, lysine acetylation often creates docking sites for bromodomain-containing "reader" proteins. This review focuses on epigenetic control of pulmonary hypertension (PH) and associated right ventricular (RV) cardiac hypertrophy and failure. Effects of small molecule HDAC inhibitors in pre-clinical models of PH are highlighted. Furthermore, we describe the recently discovered role of bromodomain and extraterminal (BET) reader proteins in the control of cardiac hypertrophy, and provide evidence suggesting that one member of this family, BRD4, contributes to the pathogenesis of RV failure. Together, the data suggest intriguing potential for pharmacological epigenetic therapies for the treatment of PH and right-sided heart failure.
authors.affiliation: Department of Medicine, Division of Cardiology, University of Colorado Denver, 12700 E. 19th Ave, Aurora, CO 80045-0508, USA.
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Stratton
authors.forename: Timothy A
authors.initials: TA
authors.lastname: McKinsey
mesh_terms: D000107:Acetylation; D000818:Animals; D004195:Disease Models, Animal; D044127:Epigenesis, Genetic; D051548:Histone Acetyltransferases / Q000378:metabolism*; D056572:Histone Deacetylase Inhibitors / Q000145:classification* / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D006976:Hypertension, Pulmonary / Q000201:enzymology*; D017380:Hypertrophy, Right Ventricular / Q000201:enzymology*; D008239:Lysine; D051381:Rats
chemical_list: D056572:Histone Deacetylase Inhibitors; D051548:Histone Acetyltransferases; D006655:Histone Deacetylases; D008239:Lysine
keywords: HDAC; RV hypertrophy; bromodomain; bromodomaine; epigenetics; hypertension pulmonaire; hypertrophie ventriculaire droite; pulmonary hypertension; épigénétique