title: Control of cardiac hypertrophy and heart failure by histone acetylation/deacetylation.
abstract: The adult heart responds to acute and chronic stresses by a remodelling process that is accompanied by myocyte hypertrophy, impaired contractility, and pump failure, often culminating in sudden death. Pathological growth and remodelling of the adult heart is often associated with the reactivation of a fetal cardiac gene program that further weakens cardiac performance. Recent studies have revealed key roles for histone deacetylases (HDACs) in the control of pathological cardiac growth. Class II HDACs associate with the MEF2 transcription factor, and other factors, to maintain normal cardiac size and function. Stress signals lead to the phosphorylation of class II HDACs and their export from the nucleus to the cytoplasm, with consequent activation of genes involved in cardiac growth. HDAC knockout mice are hypersensitive to stress signalling and develop massively enlarged hearts in response to various pathological stress stimuli due to an inability to counteract pathological signalling to MEF2. Strategies for normalizing gene expression in the failing heart by regulating HDAC phosphorylation and function represent potentially powerful therapeutic approaches.
authors.affiliation: Myogen, Inc., 757 W. 103rd Ave., Westminster, CO 80021, USA.
authors.forename: Eric N
authors.initials: EN
authors.lastname: Olson
authors.forename: Johannes
authors.initials: J
authors.lastname: Backs
authors.forename: Timothy A
authors.initials: TA
authors.lastname: McKinsey
mesh_terms: D000107:Acetylation; D000818:Animals; D006332:Cardiomegaly / Q000378:metabolism / Q000473:pathology*; D006331:Heart Diseases / Q000378:metabolism / Q000473:pathology*; D006333:Heart Failure / Q000473:pathology; D006655:Histone Deacetylases / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D008953:Models, Anatomic; D008954:Models, Biological; D010766:Phosphorylation; D014158:Transcription, Genetic
chemical_list: D006657:Histones; D006655:Histone Deacetylases