title: Roles and targets of class I and IIa histone deacetylases in cardiac hypertrophy.
abstract: Cardiac hypertrophy occurs in association with heart diseases and ultimately results in cardiac dysfunction and heart failure. Histone deacetylases (HDACs) are post-translational modifying enzymes that can deacetylate histones and non-histone proteins. Research with HDAC inhibitors has provided evidence that the class I HDACs are pro-hypertrophic. Among the class I HDACs, HDAC2 is activated by hypertrophic stresses in association with the induction of heat shock protein 70. Activated HDAC2 triggers hypertrophy by inhibiting the signal cascades of either Krüppel like factor 4 (KLF4) or inositol polyphosphate-5-phosphatase f (Inpp5f). Thus, modulators of HDAC2 enzymes, such as selective HDAC inhibitors, are considered to be an important target for heart diseases, especially for preventing cardiac hypertrophy. In contrast, class IIa HDACs have been shown to repress cardiac hypertrophy by inhibiting cardiac-specific transcription factors such as myocyte enhancer factor 2 (MEF2), GATA4, and NFAT in the heart. Studies of class IIa HDACs have shown that the underlying mechanism is regulated by nucleo-cytoplasm shuttling in response to a variety of stress signals. In this review, we focus on the class I and IIa HDACs that play critical roles in mediating cardiac hypertrophy and discuss the non-histone targets of HDACs in heart disease.
authors.affiliation: Medical Research Center for Gene Regulation, Chonnam National University Medical School, Gwangju 501-746, Republic of Korea.
authors.forename: Hae Jin
authors.initials: HJ
authors.lastname: Kee
authors.forename: Hyun
authors.initials: H
authors.lastname: Kook
mesh_terms: D000818:Animals; D006332:Cardiomegaly / Q000188:drug therapy* / Q000201:enzymology*; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D000090062:Kruppel-Like Factor 4; D051379:Mice; D058990:Molecular Targeted Therapy / Q000379:methods
chemical_list: D056572:Histone Deacetylase Inhibitors; C000715467:KLF4 protein, human; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D006655:Histone Deacetylases