The Role And Mechanism Of PPAR?/? In Atherosclerotic Plaque

The First Part The Level and Role of Peroxisome PPAR?/? in the Rabbit Models of AtherosclerosisObjective: The present study was undertaken to examine the expression level and role of PPAR-?/? in atherosclerotic rabbit models induced by a high-fat diet or high-fat diet + balloon-injury.Methods: Thirty-five male New Zealand White rabbits were divided into 3 groups: control group, high-fat diet group and high-fat diet + balloon-injury group. The high-fat diet group and high-fat diet + balloon-injury group were further divided into 6-, 8- and 10-week subgroups. The control group was provided with a normal diet, the high-fat diet groups were fed a Western diet containing 2% cholesterol and 10% fat, and the high-fat diet + balloon-injury groups received the Western diet and balloon-injury. Real-time quantitative PCR analysis was used to detect PPAR?/? and MCP-1m RNA, immunohistochemistry was used to measure PPAR?/? protein, and western blot analysis was used to examine expression of PPAR?/? and MCP-1 protein. Levels of TNF-?, IL-10, and MCP-1in serum of rabbits were measured by enzyme-linked immunosorbent assay(ELISA).Results: PPAR?/? protein and m RNA were significantly increased in the high-fat diet groups and high-fat diet + balloon-injury groups as compared with the control group(P<0.01). Furthermore, the expression of PPAR?/? were much higher in the high-fat diet + balloon-injury groups than the high-fat diet groups at the same time point(P<0.01). In addition, there were significant differences of MCP-1 protein and m RNA among different groups(P<0.01), except the high-fat 6-week group(P>0.05). Concentrations of TNF?, IL-10, and MCP-1in serum were markedly increased in the high-fat diet groups and high-fat diet + balloon-injury groups compared with the control group from weeks 6 to 10(P<0.01), and weeks 4(P<0.05).Conclusion: These results of the study indicate that PPAR?/? may play an important role in the progress of atherosclerosis.The Second Part The Role of Peroxisome Proliferator-activated Receptor ?/? and its Ligands in RAW264.7 Foam CellsObjective: We aimed to examine the role of PPAR?/? and its ligands GW0742 and GSK0660 in RAW264.7 foam cel s.Methods: Real-time quantitative PCR analysis was used to detect PPAR?/? and monocyte chemoattractant protein(MCP)-1 m RNA, western blot analysis(WB) was used to measure levels of PPAR?/? and MCP-1 protein. Levels of tumor necrosis factor(TNF)-?, interleukin(IL)-10 and MCP-1 in cell culture supernatant were measured by enzyme- linked immunosorbent assay(ELISA).Results: PPAR?/? protein and m RNA were gradually increased in the LPS group, ox-LDL group, model group and GW0742 group(P<0.01), and that of the GSK0660 group were significantly lower than the model group and GW0742 group(P<0.01). MCP-1protein and m RNA were significantly increased in the LPS group, ox-LDL group and model group(P<0.01), and decreased in the GW0742 group(P<0.01), while in the GSK0660 group MCP-1protein and m RNA were significantly increased and higher than the model group(P<0.01). Moreover, levels of TNF-? and MCP-1 in cell culture supernatant were risen markedly in the LPS group, ox-LDL group and model group(P<0.01), decreased in the GW0742 group(P<0.01), and risen again in the GSK0660 group(P<0.01). While IL-10 level in cell culture supernatant were risen significantly in the LPS group, ox-LDL group, model group and GW0742 group(P<0.01), and decreased in the GSK0660 group(P<0.01).Conclusion: GW0742 significantly increased the expression of PPAR?/?, reduced pro-inflammatory cytokines TNF-?, MCP-1 levels, and increased the level of antiinflammatory cytokine IL-10. However, GSK0660 played a totally opposite role.