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Relevance of vascular peroxisome proliferator‐activated receptor γ coactivator‐1α to molecular alterations in atherosclerosis
Author(s) -
ValeroMuñoz M.,
MartínFernández B.,
Ballesteros S.,
MartínezMartínez E.,
BlancoRivero J.,
Balfagón G.,
Cachofeiro V.,
Lahera V.,
de las Heras N.
Publication year - 2013
Publication title -
experimental physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.925
H-Index - 101
eISSN - 1469-445X
pISSN - 0958-0670
DOI - 10.1113/expphysiol.2012.070557
Subject(s) - endocrinology , medicine , adiponectin , coactivator , peroxisome proliferator activated receptor , peroxisome , inflammation , receptor , superoxide , endothelial dysfunction , sirtuin 1 , biology , chemistry , downregulation and upregulation , biochemistry , insulin resistance , transcription factor , diabetes mellitus , enzyme , gene
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.