Effects Of High Glucose, Advanced Glycation End Products And Drugs On The Expression Of Cyclooxygenase-2(COX-2) Of Human Umbilical Vein Endothelial Cells

Objective To investigate the effects of high glucose,advanced glycation end products(AGEs) on the expression of cyclooxygenase-2(COX-2) in cultured human umbilical vein endothelial cells(ECV304),and the intervention of NS398(a selective COX-2 inhibitor) ,Simvastatin on the COX-2 expression.Mehtods The human umbilical vein endothelial cells(ECV304) were cultured ,and the culture medium were changed every 3 days.1,ECV304 were incubated with different concentrations of glucose,AGE-bovine serum albumin(AGE-BSA) for different period,the proliferation of ECV304 was estimated by MTT method.2,ECV304 were incubated with different concentrations of glucose,AGE-bovine serum albumin(AGE-BSA) for different period,and exposed to high glucose(25mmol/L),AGE-BSA(200mg/L) in presence of different concentrations of NS398,Simvastatin for 24 hours,respectively,the mRNA of COX-2 in ECV304 were analyzed by RT-PCR.3,Prostaglandin E(2PGE2)in the culture medium were measured after stimulation with aboved factors by radioimmunoassay .Results 1,Glucose,AGE-BSA inhibited proliferation of ECV304 time- and dose- dependently;2, Glucose,AGE-BSA upregulated COX-2mRNA expression and increased the level of PGE2 in ECV304 time- and dose- dependently(P﹤0.05);3,The elevated expressions of COX-2mRNA and PGE2 in ECV304 treated with glucose,AGE-BSA could be blocked significantly by explosion to NS398,Simvastatin(P ﹤0.05).Conclusions 1,Glucose,AGE-BSA inhibited proliferation of ECV304 time- and dose- dependently,which may play a role in the development of diabetic vascular complications.2, Glucose,AGE-BSA upregulated the COX-2 mRNA expression and increased the level of PGE2 in ECV304 time- and dose- dependently,which indicates hyperglycemia,AGEs can damage endothelial cells,propagating the inflammatory cytokine cascade by upregulating COX-2/ PGE2;COX-2 may be a inflammatory mediators in the pathogenesis of diabetic vascular complications.3, The selective COX-2 inhibitors-NS398 reversed the high levels of COX-2mRNA/ PGE2 in ECV304 treated with high glucose,AGE-BSA,the results suggest that COX-2 could be the target for anti-inflammatory,therefor providing a new therapy prospective for diabetic vascular complications.4, Simvastatin reversed the high levels of COX-2mRNA/ PGE2 in ECV304 treated with high glucose,AGE-BSA,these findings suggest that downregulation of COX-2 is a new anti-inflammatory mechanism for simvastatin besides decreasing cholesterol,Simvastatin can improve endothelial function.