| Antifibrotic activity of an inhibitor of histone deacetylases in DOCA-salt hypertensive rats. | |
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MedLine Citation:
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PMID: 20180942 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND AND PURPOSE: Histone deacetylases (HDACs) silence genes by deacetylating lysine residues in histones and other proteins. HDAC inhibitors represent a new class of compounds with anti-inflammatory activity. This study investigated whether treatment with a broad spectrum HDAC inhibitor, suberoylanilide hydroxamic acid (SAHA), would prevent cardiac fibrosis, part of the cardiovascular remodelling in deoxycorticosterone acetate (DOCA)-salt rats. EXPERIMENTAL APPROACH: Control and DOCA-salt rats were treated with SAHA (25 mg x kg(-1) x day(-1) s.c.) for 32 days. Changes in cardiovascular structure and function were assessed by blood pressure in vivo and in Langendorff perfused hearts, ventricular papillary muscle and in aortic rings in vitro. Left ventricular collagen deposition was assessed by histology. KEY RESULTS: Administration of SAHA to DOCA-salt rats attenuated the following parameters: the increased concentration of over 20 pro-inflammatory cytokines in plasma, increased inflammatory cell infiltration and interstitial collagen deposition, increased passive diastolic stiffness in perfused hearts, prolongation of action potential duration at 20% and 90% of repolarization in papillary muscle, development of left ventricular hypertrophy, systolic hypertension and changes in vascular dysfunction. CONCLUSIONS AND IMPLICATIONS: The HDAC inhibitor, SAHA, attenuated the cardiovascular remodelling associated with DOCA-salt hypertensive rats and improved cardiovascular structure and function, especially fibrosis, in the heart and blood vessels, possibly by suppressing inflammation. Control of cardiac histone or non-histone protein acetylation is a potential therapeutic approach to preventing cardiac remodelling, especially cardiac fibrosis. |
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Authors:
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Abishek Iyer; Andrew Fenning; Junxian Lim; Giang T Le; Robert C Reid; Maria A Halili; David P Fairlie; Lindsay Brown |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-02-24 |
Journal Detail:
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Title: British journal of pharmacology Volume: 159 ISSN: 1476-5381 ISO Abbreviation: Br. J. Pharmacol. Publication Date: 2010 Apr |
Date Detail:
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Created Date: 2010-04-14 Completed Date: 2010-07-29 Revised Date: 2011-07-27 |
Medline Journal Info:
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Nlm Unique ID: 7502536 Medline TA: Br J Pharmacol Country: England |
Other Details:
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Languages: eng Pagination: 1408-17 Citation Subset: IM |
Affiliation:
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School of Biomedical Sciences, The University of Queensland, Brisbane, Qld, Australia. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Desoxycorticosterone Fibrosis / prevention & control* Heart / anatomy & histology, drug effects* Histone Deacetylase Inhibitors / pharmacology* Hydroxamic Acids / pharmacology Hypertension / pathology* Male Rats Rats, Wistar |
| Chemical | |
Reg. No./Substance:
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0/Histone Deacetylase Inhibitors; 0/Hydroxamic Acids; 149647-78-9/vorinostat; 64-85-7/Desoxycorticosterone |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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