title: Heart failure: the pivotal role of histone deacetylases.
abstract: Heart failure, a state in which cardiac output is unable to meet the metabolic demands of the tissues, poses a significant health burden; following an initial hospital admission with heart failure, five-year mortality is close to 50%. Cardiac hypertrophy, characterised by increased cardiomyocyte size and protein synthesis, has deleterious effects when prolonged and contributes to heart failure. Cardiac hypertrophy itself increases risk of morbidity and mortality. Histone deacetylases are chromatin modifiers which deacetylate the N-terminal tails of histones and have been implicated in common cardiac pathologies associated with hypertrophy. There are 18 histone deacetylases separated into four classes. Class I histone deacetylases interact with heat shock proteins and are pro-hypertrophic, class IIa histone deacetylases repress hypertrophy by inhibiting the activity of transcription factors such as myocyte enhancer factor 2. Histone deacetylases present an exciting new target in combating cardiac hypertrophy and progression to heart failure.
authors.affiliation: Cancer Sciences, Faculty of Medicine, Southampton General Hospital, University of Southampton, Southampton SO16 6YD, UK.
authors.forename: Ruth
authors.initials: R
authors.lastname: Hewitson
authors.forename: James
authors.initials: J
authors.lastname: Dargan
authors.forename: David
authors.initials: D
authors.lastname: Collis
authors.forename: Aneta
authors.initials: A
authors.lastname: Green
authors.forename: Narain
authors.initials: N
authors.lastname: Moorjani
authors.forename: Sunil
authors.initials: S
authors.lastname: Ohri
authors.forename: Paul A
authors.initials: PA
authors.lastname: Townsend
mesh_terms: D000107:Acetylation; D000818:Animals; D006332:Cardiomegaly / Q000201:enzymology; D002843:Chromatin / Q000378:metabolism; D006333:Heart Failure / Q000188:drug therapy / Q000201:enzymology*; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D006655:Histone Deacetylases / Q000502:physiology*; D006801:Humans; D018006:Myogenic Regulatory Factors / Q000378:metabolism; D011499:Protein Processing, Post-Translational
chemical_list: D002843:Chromatin; D056572:Histone Deacetylase Inhibitors; D018006:Myogenic Regulatory Factors; D006655:Histone Deacetylases