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Celastrol protects ischemic myocardium through heat shock response with upregulation of heme oxygenase-1.
MedLine Citation:
PMID:  25041185     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
BACKGROUND AND PURPOSE: Celastrol, a natural triterpene from plant extracts, has been used in traditional oriental medicine to treat various diseases. In this study we investigate the cardioprotective effects of Celastrol against ischemia.
EXPERIMENTAL APPROACH: Protective pathways induced by Celastrol were investigated in H9c2 rat cardiomyoblast hypoxic cultures and in a rat model of myocardial infarction followed by echocardiographic and histological analysis.
KEY RESULTS: In H9c2 cells, Celastrol triggered reactive oxygen species (ROS) formation within minutes, induced nuclear translocation of the transcription factor HSF1 resulting in a heat shock response (HSR) leading to increased expression of heat shock proteins (HSPs). ROS scavenger N-acetylcysteine reduced expression of HSP70 and HSP32 (HO-1). Celastrol significantly improved H9c2 survival under hypoxic stress, and functional analysis revealed the importance of HSF1 and HO-1 as key effectors of the HSR induced by Celastrol in promoting cytoprotection. In the rat ischemic myocardium, Celastrol treatment demonstrated improved cardiac function and reduced adverse left ventricular remodeling at 14 days. Celastrol triggered expression of cardioprotective protein HO-1 and abrogated fibrosis and infarct size. In the peri-infarct area, Celastrol reduced myofibroblast and macrophage infiltration, whilst attenuating the upregulation of TGF-β and collagen genes.
CONCLUSIONS AND IMPLICATIONS: Celastrol treatment induced a HSR through activation of HSF1 with upregulation of HO-1 as key effector promoting cardiomyocyte survival, reduction of injury and adverse remodeling with preservation of cardiac functionality. Celastrol may represent a novel potent pharmacological cardioprotective agent mimicking ischemic conditioning that could have a valuable impact in the treatment of myocardial infarct.
Authors:
S Der Sarkissian; J-F Cailhier; M Borie; L-M Stevens; L Gaboury; S Mansour; P Hamet; N Noiseux
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-7-9
Journal Detail:
Title:  British journal of pharmacology     Volume:  -     ISSN:  1476-5381     ISO Abbreviation:  Br. J. Pharmacol.     Publication Date:  2014 Jul 
Date Detail:
Created Date:  2014-7-21     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7502536     Medline TA:  Br J Pharmacol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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This article is protected by copyright. All rights reserved.
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