Relevance of vascular peroxisome proliferator-activated receptor γ coactivator-1α to molecular alterations in atherosclerosis.

New Findings •  What is the central question of this study? Does PGC-1α play a key role in vascular alterations induced by cholesterol+coconut oil diet in rabbits? •  What is the main finding and its importance? Vascular expression of PGC-1α, SIRT1 and PPARγ were reduced in atherosclerotic rabbits. Furthermore, PGC-1α correlated with processes involved in atherosclerosis (endothelial dysfunction, oxidative stress and inflammation). Reduction of PGC-1α seems to play an important role in the molecular alterations during the development of atherosclerosis. Peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) is emerging as a novel factor that plays a critical role in integrating signalling pathways in the control of cellular and systemic metabolism. We investigated the role of vascular expression of PGC-1α and related factors, such as sirtuin 1 (SIRT1), peroxisome proliferator-activated receptor γ (PPARγ) and adiponectin, during the atherosclerotic process. Endothelial function, vascular superoxide anion production and inflammatory mediators were also evaluated. This study was carried out in male New Zealand rabbits fed a diet containing 0.5% cholesterol and 14% coconut oil for 8 weeks. Animals developed mixed dyslipidaemia and atherosclerotic lesions, which were associated with endothelial dysfunction, aortic overproduction of superoxide anions and inflammation. Expression of PGC-1α, SIRT1, PPARγ and adiponectin was reduced (P < 0.05) in aorta from atherosclerotic rabbits. Levels of PGC-1α were correlated negatively (P < 0.05) with total cholesterol levels, aortic superoxide anion production and tumour necrosis factor-α expression, and positively (P < 0.05) with maximal relaxation in response to acetylcholine. The observed results suggest that PGC-1α could be considered to be a link between the main atherosclerotic processes (endothelial dysfunction, oxidation and inflammation) and alterations of other factors involved in vascular wall integrity, such as SIRT1, PPARγ and adiponectin.