title: HDAC inhibition suppresses cardiac hypertrophy and fibrosis in DOCA-salt hypertensive rats via regulation of HDAC6/HDAC8 enzyme activity.
abstract: Background : Inhibition of histone deacetylase (HDAC) was reported to suppress cardiac hypertrophy and fibrosis in various hypertrophic animal models. However, the HDAC expression profile and HDAC enzyme activity have not yet been investigated in DOCA-salt hypertensive rats. Methods : Unilaterally nephrectomized rats were implanted with DOCA strips. DOCA-salt rats then received a control diet with vehicle or valproate. We measured the expression of cardiac hypertrophic markers, class I HDACs, class II HDACs, fibrosis, and HDAC enzyme activity. Results : Here we report that sodium valproate inhibits the cardiac hypertrophy accompanied by fibrosis in the heart of chronic hypertensive rats. We show that expression of GATA6 and HDAC6 is upregulated in DOCA-salt hypertension. In addition, HDAC6 and HDAC8 enzyme activity is attenuated by sodium valproate. Conclusion : These results suggest that a novel HDAC6- and HDAC8-selective inhibitor is needed to treat or prevent pathological cardiac hypertrophy. © 2013 S. Karger AG, Basel.
authors.affiliation: Heart Research Center of Chonnam National University Hospital, Gwangju 501-757, Republic of Korea.
authors.forename: Hae Jin
authors.initials: HJ
authors.lastname: Kee
authors.forename: Eun Hui
authors.initials: EH
authors.lastname: Bae
authors.forename: Sangha
authors.initials: S
authors.lastname: Park
authors.forename: Ko Eun
authors.initials: KE
authors.lastname: Lee
authors.forename: Sang Heon
authors.initials: SH
authors.lastname: Suh
authors.forename: Soo Wan
authors.initials: SW
authors.lastname: Kim
authors.forename: Myung Ho
authors.initials: MH
authors.lastname: Jeong
mesh_terms: D000818:Animals; D006332:Cardiomegaly / Q000139:chemically induced / Q000188:drug therapy* / Q000201:enzymology*; D064791:Desoxycorticosterone Acetate / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004789:Enzyme Activation / Q000187:drug effects / Q000235:genetics; D005355:Fibrosis; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases / Q000235:genetics*; D006973:Hypertension / Q000139:chemically induced / Q000188:drug therapy* / Q000201:enzymology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012097:Repressor Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics*; D014635:Valproic Acid / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D012097:Repressor Proteins; D014635:Valproic Acid; D064791:Desoxycorticosterone Acetate; C545556:HDAC6 protein, rat; C409470:HDAC8 protein, human; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases