title: The expression and role of peroxisome proliferator-activated receptor             α in atherosclerosis.
abstract: Peroxisome proliferator-activated receptor α (PPAR-α) has been detected in the liver, kidney, heart and skeletal muscle. The expression and mechanism of PPAR-α in atherosclerosis remains unclear. The present study was undertaken in order to examine the expression and role of PPAR-α in programmed atherosclerosis induced by a high‑fat diet and balloon-injury in rabbits. Rabbits were randomly divided into 3 groups: control, high-fat diet and high-fat diet+balloon‑injury groups. The high-fat diet and high-fat diet+balloon-injury groups were further divided into 6-, 8- and 10-week groups. Real-time quantitative PCR analysis was used to detect PPAR-α mRNA and immunohistochemistry (IHC) and western blot analysis were used to examine PPAR-α protein expression. Tumor necrosis factor (TNF)-α, interleukin (IL)-10 and P-selectin levels in the rabbits were measured by enzyme-linked immunosorbent assay (ELISA). In the high-fat or high-fat diet+balloon-injury groups, the vascular thickness was markedly higher than in the control group (P<0.01). PPAR-α protein and mRNA were significantly increased in the high-fat diet group as compared with the control group (P<0.01). Furthermore, there were marked changes from 6 to 10 weeks in the high-fat diet group (P<0.01). Compared with the control group, PPAR-α protein and mRNA were increased in the high-fat diet+balloon-injury group (P<0.01). There were significant differences of PPAR-α protein and mRNA at various time points in the high-fat diet+balloon‑injury group, as shown by real-time quantitative PCR and IHC (P<0.01). As shown by western blotting, there were no differences between the high-fat diet + balloon-injury 8- and 10-week groups (P>0.05). In those arteries that were occluded by ≥60%, PPAR-α expression was lower than that in the arteries which were occluded <60% in the high‑fat diet+balloon-injury 10-week group. In the high-fat diet and high-fat diet+balloon-injury groups, the levels of IL-10, TNF-α and P-selectin were upregulated compared with the control group. However, from weeks 8 to 10, TNF-α and P-selectin were decreased and IL-10 was still increased in the high-fat diet+balloon-injury group. The results of this study demonstrate that PPAR-α has preventive effects on atherosclerosis, which may be related to the regulation of inflammation.
authors: Department of Cardiology, Shanghai First People's Hospital, College of Medicine, Shanghai Jiaotong University, Shanghai 200080, PR China.
authors: Wen
authors: W
authors: Gao
authors: Wei
authors: W
authors: Xu
authors: Hongli
authors: H
authors: Li
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000378:metabolism* / Q000473:pathology; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000473:pathology; D016753:Interleukin-10 / Q000097:blood; D008297:Male; D019007:P-Selectin / Q000097:blood; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D019007:P-Selectin; D047493:PPAR alpha; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10