PPAR-alpha activation protects myocardium against ischemia/reperfusion injury in isolated rat heart (ESC 2012) - May 15, 2012 - Presentation time: 20/05/2012 08:30 AM -12:30 PM; Selective activation of PPAR-alpha attenuated I/R injury & oxidative stress in left ventricle myocardium; Protective effects of WY were reversed by wortmannin indicating that activation of PI3K/Akt may be involved in protection against I/R injury in the rat heart conferred by PPAR-alpha agonists
Preclinical-animal • Dyslipidemia
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European Society of Cardiology Heart Failure 2012 (ESC 2012): 19-22 May, 2012: Belgrade, Serbia.
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Peroxisome proliferator-activated receptor-alpha (PPAR-alpha) is a nuclear ligand-activated transcription factor expressed in a number of tissues including the myocardium. PPAR-alpha regulates the metabolism of lipoproteins and fatty acids, as well as the transcription of several factors involved in inflammatory response and oxidative stress. Growing evidence suggests that PPAR-alpha activation may reduce ischemia/reperfusion (I/R) injury through metabolic and anti-inflammatory effects. Several studies have shown protective effects of PPAR-alpha agonists against I/R injury similar to preconditioning that may be related to phosphatidylinositol 3-kinase (PI3K)/Akt pathway. However, the role of PPAR-alpha in acute I/R injury remains unclear. Therefore, the aim of the study was to evaluate the effects of PPAR-alpha activation and simultaneous inhibition of PI3K/Akt on I/R injury in langendorff-perfused isolated rat hearts. Male wistar rats were divided into four groups: WYC -- pretreated with a PPAR-alpha agonist WY14643 (WY; 3mg/kg/day, 5 days, p.o.), CW -- given PI3K inhibitor Wortmannin (W; 100 nM) 15 min before ischemia in perfusion medium, WYW -- pretreated with WY and W, C -- untreated controls. All hearts were subjected to 30-min global ischemia followed by 2-h reperfusion for the determination of infarct size (IS, in % of area at risk, TTC staining), recovery of contractile function and reperfusion-induced arrhythmias. Gene expression of PPAR-alpha (RT-PCR) as well as levels of conjugated dienes (CD) were detected in the heart samples before ischemia and after 40 min of reperfusion. Two-fold increased cardiac mRNA levels of PPAR-alpha at baseline were preserved after I/R in WYC in contrast to their marked downregulation in C. Levels of CD were lower after I/R in WYC group. Pretreatment with WY significantly improved postischemic restoration of functional parameters (LVDP 60 ± 9% of baseline values vs. 24 ± 3% in C), and reduced IS and incidence of ventricular fibrillation by 51% and 53%, respectively (P selective activation of PPAR-alpha attenuated I/R injury and oxidative stress in left ventricle myocardium. Protective effects of WY were reversed by wortmannin indicating that activation of PI3K/Akt may be involved in protection against I/R injury in the rat heart conferred by PPAR-alpha agonists.
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