Objective To investigate the cellular signal transduction pathway during vascular smooth muscle cell (VSMC)
proliferation
and cytokins
secretion stimulated by oxidized low density lipoprotein (oxLDL) and by the intervention effect of rapamycin. Methods Rabbit aortic VSMC was cultured in 7 groups. Cell
proliferation was determined by measuring cell number and mitochondrial dehydrogenase (MD) activity (MTT assay). The level of tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6) and interleukin-8 (IL-8) were tested by ELISA method. Western blot was used to detect the protein expression of protein kinase B(PKB). Immunoprecipitation and radioactivity of γ 32 P incorporated into it's specific substrate histon H 2B were utilized to determine the PKB activation. Results oxLDL increased cell number and MD activity to 1.62-3.2 fold, the secretion of TNF-α, IL-6 and IL-8 to 3-5 fold,and PKB activity up to 11.8 fold. LDL had no effect as oxLDL did. WT and rapamycin markedly inhibited VSMC proliferation, cytokins secretion and PKB activity and reversed all the above effects of oxLDL. Conclusion PI 3K/PKB signal transduction system is one of the crucial signal pathway involved in rabbit VSMC proliferation and secretion of TNF-α, IL-6 and IL-8 stimulated with or without oxLDL. Rapamycin may exsert it's regulating effect on biological functions of rabbit VSMCs by inhibiting PKB activition. <