title: Relevance of vascular peroxisome proliferator-activated receptor γ coactivator-1α to molecular alterations in atherosclerosis.
abstract: 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.
authors: Department of Physiology, School of Medicine, Universidad Complutense, Madrid, Spain.
authors: M
authors: M
authors: Valero-Muñoz
authors: B
authors: B
authors: Martín-Fernández
authors: S
authors: S
authors: Ballesteros
authors: E
authors: E
authors: Martínez-Martínez
authors: J
authors: J
authors: Blanco-Rivero
authors: G
authors: G
authors: Balfagón
authors: V
authors: V
authors: Cachofeiro
authors: V
authors: V
authors: Lahera
authors: N
authors: N
authors: de las Heras
mesh_terms: D052242:Adiponectin / Q000096:biosynthesis; D000818:Animals; D001011:Aorta / Q000378:metabolism; D050197:Atherosclerosis / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D018955:CD36 Antigens / Q000096:biosynthesis; D002791:Cholesterol, Dietary; D000074263:Coconut Oil; D004730:Endothelium, Vascular / Q000187:drug effects; D008055:Lipids / Q000097:blood; D008297:Male; D047495:PPAR gamma / Q000096:biosynthesis; D010938:Plant Oils; D011817:Rabbits; D056564:Sirtuin 1 / Q000096:biosynthesis; D014157:Transcription Factors / Q000378:metabolism*; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis; D014664:Vasodilation
chemical_list: D052242:Adiponectin; D018955:CD36 Antigens; D002791:Cholesterol, Dietary; D008055:Lipids; D047495:PPAR gamma; D010938:Plant Oils; D014157:Transcription Factors; D019010:Vascular Cell Adhesion Molecule-1; D056564:Sirtuin 1; D000074263:Coconut Oil