title: Role of peroxisome proliferator-activated receptor α in atherosclerosis.
abstract: Atherosclerosis is an inﬂammatory disease involving the immune response. In addition to lowering the cholesterol level, the peroxisome proliferator-activated receptor α (PPAR-α) can prevent atherosclerosis via its pleiotropic anti-inflammatory effects. However, the role of PPAR-α in modulating inflammatory progression of atherosclerosis has rarely been studied. Thus, we aimed to investigate the role of PPAR-α in atherosclerosis by evaluating the expression of inflammatory cytokines induced by PPAR-α in an in vivo rabbit model. New Zealand White rabbits were randomly divided into 5 groups: control, high-fat diet + balloon injury, high-fat diet + balloon injury + placebo, high-fat diet + balloon injury + fenofibrate, and high-fat diet + balloon injury + WY-14643. The femoral arteries of rabbits were balloon-injured after initiation of the high-fat diet and before administration of fenofibrate, WY-14643 or placebo solution. Atherosclerosis was induced by high-fat diet and balloon angioplasty, and the vessel wall lumen occlusion was determined by measuring the stenosis rate. PPAR-α gene expression was examined by quantitative polymerase chain reaction analysis. The cellular localization and distribution of PPAR-α was observed by immunohistochemistry, and its protein level was assessed by western blot analysis. The production of interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α) and P-selectin, which are major inflammatory factors involved in atherosclerosis, was monitored by an enzyme-linked immunosorbent assay (ELISA). Treatment with PPAR-α agonists (fenofibrate or WY-14643) reduced the vascular occlusion rate, as compared to the high-fat diet + balloon injury and the placebo groups. Furthermore, the expression of PPAR-α at both the protein and the mRNA level was increased in the fenofibrate and WY-14643 groups. According to the results, the TNF-α and P-selectin levels were reduced in the fenofibrate and WY-14643 groups. These results suggest that PPAR-α activation can attenuate the effects of atherosclerosis by inhibiting the expression of major inflammatory factors in a rabbit atherosclerosis model.
authors.affiliation: Department of Cardiology, Shanghai First People's Hospital, College of Medicine, Shanghai Jiaotong University, Shanghai 200080, P.R. China.
authors.forename: Heng
authors.initials: H
authors.lastname: Cao
authors.affiliation: Department of Cardiology, Shanghai First People's Hospital, College of Medicine, Shanghai Jiaotong University, Shanghai 200080, P.R. China.
authors.forename: Gao
authors.initials: G
authors.lastname: Wen
authors.affiliation: Department of Cardiology, Shanghai First People's Hospital, College of Medicine, Shanghai Jiaotong University, Shanghai 200080, P.R. China.
authors.forename: Hongli
authors.initials: H
authors.lastname: Li
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D015870:Gene Expression; D007150:Immunohistochemistry; D018836:Inflammation Mediators / Q000097:blood; D008297:Male; D019007:P-Selectin / Q000097:blood; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport; D011817:Rabbits
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D019007:P-Selectin; D047493:PPAR alpha