Roles of HDAC2 and HDAC8 in Cardiac Remodeling in Renovascular Hypertensive Rats and the Effects of Valproic Acid Sodium.
Recent studies indicate that histone deacetylases (HDACs) activity is associated with the development and progression of cardiac hypertrophy. In this study, we investigated the effects of a HDACs inhibitor, valproic acid sodium (VPA), on cardiac remodeling and the differential expression of HDACs in left ventricles (LVs) of renovascular hypertensive rats. Renovascular hypertension was induced in rats by the two-kidney two-clip (2K2C) method. Cardiac remodeling, heart function and the differential expression of HDACs were examined at different weeks after 2K2C operation. The effects of VPA on cardiac remodeling, the expressions of HDACs, transforming growth factor-beta 1 (TGF-β1) and connective tissue growth factor (CTGF) in LV were investigated. The expressions of atrial natriuretic factor, β-myosin heavy chain, HDAC2 and HDAC8 increased in LV of 2K2C rats at 4, 8, 12 weeks after operation. Cardiac dysfunction, cardiac hypertrophy and fibrosis were markedly attenuated by VPA treatment in 2K2C rats. Further studies revealed that VPA inhibited the expressions of HDAC2, HDAC8, TGF-β1 and CTGF in LV of 2K2C rats. In summary, these data indicate that HDAC2 and HDAC8 play a key role in cardiac remodeling in renovascular hypertensive rats and that VPA attenuates hypertension and cardiac remodeling. The effect of VPA is possibly exerted via decreasing HDAC2, HDAC8, TGF-β1 and CTGF expressions in LV of 2K2C rats.
Laboratory of Pharmacology and Molecular Biology, Medical College, Henan University of Science and Technology, Luoyang, PR China.
Rui-Fang
RF
Li
Shan-Shan
SS
Cao
Wei-Jin
WJ
Fang
Ying
Y
Song
Xue-Ting
XT
Luo
Hong-Yun
HY
Wang
Jian-Gang
JG
Wang
D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D056464:Histone Deacetylase 2 / Q000037:antagonists & inhibitors / Q000502:physiology*; D006655:Histone Deacetylases / Q000502:physiology*; D006978:Hypertension, Renovascular / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D008297:Male; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D016896:Treatment Outcome; D014635:Valproic Acid / Q000494:pharmacology / Q000627:therapeutic use*; D020257:Ventricular Remodeling / Q000187:drug effects* / Q000502:physiology
D004791:Enzyme Inhibitors; D014635:Valproic Acid; C000603105:HDAC8 protein, mouse; C533426:Hdac2 protein, rat; D056464:Histone Deacetylase 2; D006655:Histone Deacetylases