Document Detail

Cardiac HDAC6 catalytic activity is induced in response to chronic hypertension.
MedLine Citation:
PMID:  21539845     Owner:  NLM     Status:  MEDLINE    
Small molecule histone deacetylase (HDAC) inhibitors block adverse cardiac remodeling in animal models of heart failure. The efficacious compounds target class I, class IIb and, to a lesser extent, class IIa HDACs. It is hypothesized that a selective inhibitor of a specific HDAC class (or an isoform within that class) will provide a favorable therapeutic window for the treatment of heart failure, although the optimal selectivity profile for such a compound remains unknown. Genetic studies have suggested that class I HDACs promote pathological cardiac remodeling, while class IIa HDACs are protective. In contrast, nothing is known about the function or regulation of class IIb HDACs in the heart. We developed assays to quantify catalytic activity of distinct HDAC classes in left and right ventricular cardiac tissue from animal models of hypertensive heart disease. Class I and IIa HDAC activity was elevated in some but not all diseased tissues. In contrast, catalytic activity of the class IIb HDAC, HDAC6, was consistently increased in stressed myocardium, but not in a model of physiologic hypertrophy. HDAC6 catalytic activity was also induced by diverse extracellular stimuli in cultured cardiac myocytes and fibroblasts. These findings suggest an unforeseen role for HDAC6 in the heart, and highlight the need for pre-clinical evaluation of HDAC6-selective inhibitors to determine whether this HDAC isoform is pathological or protective in the setting of cardiovascular disease.
Douglas D Lemon; Todd R Horn; Maria A Cavasin; Mark Y Jeong; Kurt W Haubold; Carlin S Long; David C Irwin; Sylvia A McCune; Eunhee Chung; Leslie A Leinwand; Timothy A McKinsey
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-04-23
Journal Detail:
Title:  Journal of molecular and cellular cardiology     Volume:  51     ISSN:  1095-8584     ISO Abbreviation:  J. Mol. Cell. Cardiol.     Publication Date:  2011 Jul 
Date Detail:
Created Date:  2011-05-27     Completed Date:  2011-09-14     Revised Date:  2014-09-22    
Medline Journal Info:
Nlm Unique ID:  0262322     Medline TA:  J Mol Cell Cardiol     Country:  England    
Other Details:
Languages:  eng     Pagination:  41-50     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Elsevier Ltd. All rights reserved.
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MeSH Terms
Adenoviridae / genetics
Cardiovascular Diseases
Cells, Cultured
Heart Ventricles / enzymology
Histone Deacetylase Inhibitors / pharmacology
Histone Deacetylases / biosynthesis,  genetics,  metabolism*
Hypertension / enzymology*,  pathology
Myocardium / enzymology*
Myocytes, Cardiac / enzymology
Polymerase Chain Reaction
Protein Isoforms
RNA Interference
RNA, Small Interfering
Rats, Sprague-Dawley
Signal Transduction
Ventricular Remodeling
Grant Support
Reg. No./Substance:
0/Histone Deacetylase Inhibitors; 0/Protein Isoforms; 0/RNA, Small Interfering; EC protein, mouse; EC Deacetylases

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