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Inhibition of histone deacetylation blocks cardiac hypertrophy induced by angiotensin II infusion and aortic banding

Cited 240 time in Web of Science Cited 241 time in Scopus
Authors
Kee, Hae Jin; Sohn, Il Suk; Nam, Kwang Il; Park, Jong Eun; Qian, Yong Ri; Yin, Zhan; Ahn, Youngkeun; Jeong, Myung Ho; Bang, Yung-Jue; Kim, Nacksung; Kim, Jong-Keun; Kim, Kyung Keun; Epstein, Jonathan A; Kook, Hyun
Issue Date
2005-12-29
Publisher
American Heart Association
Citation
Circulation. 2006 Jan 3;113(1):51-9. Epub 2005 Dec 27.
Keywords
Angiotensin II/administration & dosage/*pharmacologyAnimalsAortic Valve Stenosis/*complicationsBiological Markers/analysisCardiomegaly/*chemically induced/*drug therapy/prevention & controlDisease Models, AnimalDrug Evaluation, PreclinicalEnzyme Inhibitors/administration & dosage/*pharmacology/therapeutic useHistone Deacetylases/*antagonists & inhibitorsMaleMiceMice, Inbred StrainsRatsRats, Sprague-DawleyTreatment Outcome
Abstract
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.
ISSN
1524-4539 (Electronic)
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16380549

http://hdl.handle.net/10371/29561
DOI
https://doi.org/10.1161/CIRCULATIONAHA.105.559724
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College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
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