Document Detail

Reperfusion-triggered stress protein response in the myocardium is blocked by post-conditioning. Systems biology pathway analysis highlights the key role of the canonical aryl-hydrocarbon receptor pathway.
MedLine Citation:
PMID:  22851653     Owner:  NLM     Status:  Publisher    
AimsIschaemic post-conditioning (IPost-Co) exerts cardioprotection by diminishing ischaemia/reperfusion injury. Yet, the mechanisms involved in such protection remain largely unknown. We have investigated the effects of IPost-Co in cardiac cells and in heart performance using molecular, proteomic and functional approaches.Methods and resultsPigs underwent 1.5 h mid-left anterior descending balloon occlusion and then were sacrificed without reperfusion (ischaemia; n= 7), subjected to 2.5 h of cardiac reperfusion and sacrificed (n= 5); or subjected to IPost-Co before reperfusion and sacrificed 0.5 h (n= 4) and 2.5 h (n= 5) afterwards. A sham-operated group was included (n= 4). Ischaemic and non-ischaemic myocardium was obtained for molecular/histological analysis. Proteomic analysis was performed by two-dimensional electrophoresis followed by matrix-assisted laser desorption/ionization-time-of-flight identification. Potential protein networks involved were identified by bioinformatics and Ingenuity Pathway Analysis (IPA). Cardiac function was assessed by echocardiography. IPost-Co diminished (up to 2.5 h) reperfusion-induced apoptosis of both the intrinsic and extrinsic pathways whereas it did not affect reperfusion-induced Akt/mammalian target of rapamycin (mTOR)/P70(S6K) activation. Proteomic studies showed that IPost-Co reverted 43% of cardiac cytoplasmic protein changes observed during ischaemia and ischaemia + reperfusion. Systems biology assessment revealed significant changes in the aryl-hydrocarbon receptor (AhR) pathway (cell damage related). Bioinformatic data were confirmed since the expression of HSP90, AhR, ANRT, and β-tubulin (involved in AhR-signalling transduction) were accordingly modified after IPost-Co. IPost-Co rescued 52% of the left ventricle-at-risk compared with reperfusion alone and resulted in a ≈30% relative improvement in left ventricular ejection fraction (P <0.05).ConclusionIPost-Co improves cardiac function post-myocardial infarction and reduces reperfusion-induced cell damage by down-regulation of the AhR-signalling transduction pathway ultimately leading to infarct size reduction.
Gemma Vilahur; Judit Cubedo; Laura Casani; Teresa Padro; Manel Sabate-Tenas; Juan J Badimon; Lina Badimon
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-7-31
Journal Detail:
Title:  European heart journal     Volume:  -     ISSN:  1522-9645     ISO Abbreviation:  Eur. Heart J.     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-8-1     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8006263     Medline TA:  Eur Heart J     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Cardiovascular Research Center, CSIC-ICCC, Hospital de la Santa Creu i Sant Pau and CIBEROBN-Pathophysiology of Obesity and Nutrition, c/Sant Antoni MªClaret 167, 08025 Barcelona, Spain.
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