The expression and role of peroxisome proliferator-activated receptor α in atherosclerosis

Gao,Wen; Xu,Wei; Li,Hongli

doi:10.3892/mmr.2013.1282

The expression and role of peroxisome proliferator-activated receptor α in atherosclerosis

Authors:
- Wen Gao
- Wei Xu
- Hongli Li
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Affiliations: Department of Cardiology, Shanghai First People's Hospital, College of Medicine, Shanghai Jiaotong University, Shanghai 200080, P.R. China, Department of Interventional Radiology, the Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China
Published online on: January 21, 2013 https://doi.org/10.3892/mmr.2013.1282
Pages: 862-868

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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.

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