title: Histone deacetylases as therapeutic targets--from cancer to cardiac disease.
abstract: Heart failure is a major public health problem in western society. Recently, agents that inhibit histone deacetylase (HDAC) enzymes were developed and approved by the FDA as anticancer agents. This breakthrough has provided the motivation to develop more potent and more selective HDAC inhibitors and to target other pathologic conditions with these drugs. Here we review experimental evidence showing that these drugs may be beneficial in preventing cardiac hypertrophy and heart failure. Several lines of evidence show that inhibitors of Class I HDACs can blunt cardiac hypertrophy and preserve cardiac function in several small animal models. In contrast, Class IIa HDACs appear to be suppressors of hypertrophy, though experimental data with small molecule blockers of this class is largely lacking. The effects of HDAC inhibition in cardiac diseases, the cell population in the heart that is targeted by HDAC blockers, as well as the relative roles of specific HDACs are still under intense investigation.
authors.affiliation: The Bruce Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, POB 9649, Haifa 31096, Israel.
authors.forename: Alon
authors.initials: A
authors.lastname: Abend
authors.affiliation: The Bruce Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, POB 9649, Haifa 31096, Israel. Electronic address: ikehat@tx.technion.ac.il.
authors.forename: Izhak
authors.initials: I
authors.lastname: Kehat
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage; D016503:Drug Delivery Systems / Q000379:methods*; D006331:Heart Diseases / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D056572:Histone Deacetylase Inhibitors / Q000008:administration & dosage*; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases
keywords: Heart failure; Histone deacetylases; Histone deacetylases inhibitors; Hypertrophy