Document Detail

Inhibition of histone deacetylation blocks cardiac hypertrophy induced by angiotensin II infusion and aortic banding.
MedLine Citation:
PMID:  16380549     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: A number of distinct stress signaling pathways in myocardium cause cardiac hypertrophy and heart failure. Class II histone deacetylases (HDACs) antagonize several stress-induced pathways and hypertrophy. However, cardiac hypertrophy induced by transgenic overexpression of the homeodomain only protein, HOP, can be prevented by the nonspecific HDAC inhibitors trichostatin A and valproic acid, suggesting that alternate targets that oppose class II HDAC function might exist in myocardium. We tested the effects of several HDAC inhibitors, including a class I HDAC-selective inhibitor, SK-7041, on cardiac hypertrophy induced by angiotensin II (Ang II) treatment or aortic banding (AB). METHODS AND RESULTS: Cardiac hypertrophy was induced by chronic infusion of Ang II or by AB in mice or rats and evaluated by determining the ratio of heart weight to body weight or to tibia length, cross-sectional area, or echocardiogram. Cardiac hypertrophy induced by Ang II or AB for 2 weeks was significantly reduced by simultaneous administration of trichostatin A, valproic acid, or SK-7041. Echocardiogram revealed that exaggerated left ventricular systolic dimensions were relieved by HDAC inhibitors. HDAC inhibitors partially reversed preestablished cardiac hypertrophy and improved survival of AB mice. The expressions of atrial natriuretic factor, alpha-tubulin, beta-myosin heavy chain, and interstitial fibrosis were reduced by HDAC inhibition. CONCLUSIONS: These results suggest that the predominant effect of HDAC inhibition, mainly mediated by class I HDACs, is to prevent cardiac hypertrophy in response to a broad range of agonist and stretch stimuli.
Hae Jin Kee; Il Suk Sohn; Kwang Il Nam; Jong Eun Park; Yong Ri Qian; Zhan Yin; Youngkeun Ahn; Myung Ho Jeong; Yung-Jue Bang; Nacksung Kim; Jong-Keun Kim; Kyung Keun Kim; Jonathan A Epstein; Hyun Kook
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2005-12-27
Journal Detail:
Title:  Circulation     Volume:  113     ISSN:  1524-4539     ISO Abbreviation:  Circulation     Publication Date:  2006 Jan 
Date Detail:
Created Date:  2006-01-04     Completed Date:  2006-02-22     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  United States    
Other Details:
Languages:  eng     Pagination:  51-9     Citation Subset:  AIM; IM    
Department of Pharmacology, Research Institute of Medical Sciences and Medical Research Center for Gene Regulation, Chonnam National University Medical School, Gwangju, South Korea.
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MeSH Terms
Angiotensin II / administration & dosage,  pharmacology*
Aortic Valve Stenosis / complications*
Biological Markers / analysis
Cardiomegaly / chemically induced*,  drug therapy*,  prevention & control
Disease Models, Animal
Drug Evaluation, Preclinical
Enzyme Inhibitors / administration & dosage,  pharmacology*,  therapeutic use
Histone Deacetylase Inhibitors*
Mice, Inbred Strains
Rats, Sprague-Dawley
Treatment Outcome
Reg. No./Substance:
0/Biological Markers; 0/Enzyme Inhibitors; 0/Histone Deacetylase Inhibitors; 11128-99-7/Angiotensin II

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