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PPAR-alpha activation as a preconditioning-like intervention in rats in vivo confers myocardial protection against acute ischaemia-reperfusion injury: involvement of PI3K-Akt.
MedLine Citation:
PMID:  22809038     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Peroxisome proliferator-activated receptors (PPAR) regulate the expression of genes involved in lipid metabolism, energy production, and inflammation. Their role in ischaemia-reperfusion (I/R) is less clear, although research indicates involvement of PPARs in some forms of preconditioning. This study aimed to explore the effects of PPAR-α activation on the I/R injury and potential cardioprotective downstream mechanisms involved. Langendorff-perfused hearts of rats pretreated with the selective PPAR-α agonist WY-14643 (WY, pirinixic acid; 3 mg·(kg body mass)·day(-1); 5 days) were subjected to 30 min ischaemia - 2 h reperfusion with or without the phosphatidylinositol 3-kinase (PI3K)-Akt inhibitor wortmannin for the evaluation of functional (left ventricular developed pressure, LVDP) recovery, infarct size (IS), and reperfusion-induced arrhythmias. A 2-fold increase in baseline PPAR-α mRNA levels (qPCR) in the WY-treated group and higher post-I/R PPAR-α levels compared with those in untreated controls were accompanied by similar changes in the expression of PPAR-α target genes PDK4 and mCPT-1, regulating glucose and fatty acid metabolism, and by enhanced Akt phosphorylation. Post-ischaemic LVDP restoration in WY-treated hearts reached 60% ± 9% of the pre-ischaemic values compared with 24% ± 3% in the control hearts (P < 0.05), coupled with reduced IS and incidence of ventricular fibrillation that was blunted by wortmannin. Results indicate that PPAR-α up-regulation may confer preconditioning-like protection via metabolic effects. Downstream mechanisms of PPAR-α-mediated cardioprotection may involve PI3K-Akt activation.
Authors:
Táňa Ravingerová; Slávka Carnická; Martina Nemčeková; Veronika Ledvényiová; Adriana Adameová; Tara Kelly; Eleftheria Barlaka; Eleftheria Galatou; Vinoth Kumar Megraj Khandelwal; Antigone Lazou
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-7-18
Journal Detail:
Title:  Canadian journal of physiology and pharmacology     Volume:  -     ISSN:  1205-7541     ISO Abbreviation:  -     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-7-19     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0372712     Medline TA:  Can J Physiol Pharmacol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
a Institute for Heart Research, Slovak Academy of Sciences and Centre of Excellence of SAS NOREG, POB 104, Dubravská cesta 9, 840 05 Bratislava, Slovak Republic.
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