Training-induced anti-atherosclerotic effects are associated with increased vascular PPARgamma expression in apolipoprotein E-deficient mice

Aim: Physical exercise prevents cardiovascular risk and atherosclerosis lesions. However, the molecular aspects are still unknown. Vascular peroxisome proliferator-activated receptors (PPARs) exert anti-atherogenic effects. The aim of this study was to determine whether exercise-induced anti-atherosclerotic effect is associated with change in PPARs vascular expression in apolipoprotein E-deficient (ApoE(-/-)) mice. Methods: Male ApoE(-/-) mice were fed with a high-fat diet and randomized into two groups: one trained group undergoing swimming training for 3 months and one sedentary group. Sedentary and trained C57BL/6J mice were used as control. mRNA of PPAR-alpha, PPAR-beta/delta and PPAR-gamma was measured in aorta by quantitative PCR. mRNA of pro-(TNF-alpha, IL-1 beta) and anti-inflammatory (IL-10, IL-1Ra) cytokines was also measured. Results: Atherosclerotic lesion size was significantly reduced in trained ApoE(-/-) mice compared to sedentary ones. In contrast, reduction of atherosclerotic lesion size was not observed in trained ApoE(-/-) mice supplied with BADGE, an antagonist of PPAR-gamma. Exercise training significantly increased PPAR-gamma expression in aorta. PPAR-gamma expression was inversely correlated with the atherosclerotic plaque area. Aortic PPAR-alpha and PPAR-beta/delta mRNA expressions were not changed in response to exercise training. Atherosclerosis increased the aortic mRNA expression of TNF-alpha, IL-1 beta, IL-10 and IL-1Ra. Exercise training decreased aortic IL-1 beta mRNA expression in ApoE(-/-) mice, but did not change expression of TNF-alpha, IL-10 and IL-1Ra. IL-1 beta mRNA expression was also significantly lower in atherosclerosis lesions from trained ApoE(-/-) compared with those from sedentary ones. Conclusions: Exercise training increases vascular PPAR-gamma expression in ApoE(-/-) mice that could potentially underlie training-related beneficial effects on atherosclerosis.