Mechanism study of Cyclooxygenase-2 Expression in vascular smooth muscle cells after balloon angioplasty in rabbits and Selective Cydooxygenase-2 Inhibitor on Proliferation and Apoptosis of VSMC

Objective The purpose of this research was to investigate the COX-2 mRNA level in vascular smooth muscle cell after balloon angioplasty in rabbits and the influence of selective COX-2 inhibitor -NS-398 on proliferation and apoptosis of VSMC,which reveals the potential mechanism of NS-398 effect on VSMC.Methods We assessed COX-2 mRNA in 20 cases of VSMC and adjacent normal tissue by RT- PCR.;Then it was treated with NS-398(a selective COX-2 inhibitor)at different times.MTT assay and flow cytometry were used to measure the proliferation and apoptosis.The expression of Cyclin D1 and Bcl-2 were measured by western blot.Results COX-2 mRNA level were increased in VSMC compared with adjacent normal mucosa(P＜0.05),the median values were 2.42-fold,The ratios of S and G2/M percentage,Cyc- lin D1 and Bcl-2 expression between blank group and NS-398-treated group were 1.31 and 1.62(P＜0.01),2.37 and 3.81(P＜0.01),respectively.NS-398-treated group were inhibited the cells proliferation and induced apoptosis in a dose,time-dependent manner and resulted in significant downregulation of Cyclin D1 and Bcl-2.Conclusions Our results show that overexpression of COX-2 may play a critical role in the development of VSMC after balloon angioplasty.Selective COX-2 inhibitor NS-398 may inhibit the prolifera- tion and induce apoptosis of VSMC through decreasing expression of Cyclin D1 and Bcl-2.It may be a new target of selective COX-2 inhibitor effect on restenosis of Percutaneous Coronary Intervention.