Abstract: Abstract: Objective To investigate the role of cyclin-dependent kinases 5 (CDK5) - mediated PPARγ phosphorylation in atherosclerosis. Methods Raw264.7 macrophages were induced by ox-LDL to differentiate into foam cells, and then CDK5 inhibitor was used as the intervent. The experimental cells were divided into control group (C group), ox-LDL group (O group, 50 mg/L ox-LDL) and roscovitine group (50 mg/L ox-LDL+15 μmol/L Roscovitine). Expressions of pPPARγ, tPPARγ, p35 and CDK5 protein were detected by Western blot assay. Lipid accumulation was analyzed by oil red O staining and isopropyl alcohol extraction experiments. Levels of cholesterol content in macrophages were measured by enzymatic method. Expression of ox-LDL uptake related genes CD36, SR-A1 and cholesterol efflux related genes ABCA1 and ABCG1 were detected by RT-PCR. Results After ox-LDL induction, the ratios of pPPARγ/tPPARγ and p35/CDK5 significantly increased, and lipid accumulation, total cholesterol content, free cholesterol content and the ratio of cholesterol ester / total cholesterol were up-regulated significantly in O group compared with those of C group (P＜0.05). RT-PCR showed that expression levels of ox-LDL uptake-related genes CD36 and SR-A1 mRNA increased, while the expression levels of cholesterol efflux-related genes ABCA1 and ABCG1 decreased in O group (P＜0.05). After intervention with CDK5 inhibitor, the above indicators showed the opposite trend compared with those of O group (P＜0.05). Conclusion CDK5/ pPPARγ pathway is involved in the formation of foam cells in atherosclerosis.

Key words: atherosclerosis, foam cells, cyclin-dependent kinase 5, peroxisome proliferator-activated receptors, CD36, SR-A1, ABCA1, ABCG1