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.