Expression of HGF/c-Met during proliferation and apoptosis of VSMC in rabbits

Objective To investigate the hepatocyte growth factor(HGF)receptor c-Met mRNA level in vascu- lar smooth muscle cells(VSMCs)after balloon angioplasty in rabbits and reveal the potential effect of c-Met on proliferation and apoptosis of VSMCs.Methods c-Met mRNA in VSMCs and adjacent normal tissue from ab- dominal aorta of 36 tabbits were measured by RT-PCR. Cultured VSMCs of rabbits in vitro were treated with NK-4(a selective c-Met inhibitor)at different time.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 C-Met mRNA level was increased by 2.42 times in average in VSMCs compared with that in adjacent normal vessel wall(P＜0.01).The ratios of S and G2/M percentages of control group to those of NK-4-treated group were 1.31 and 1.62(P＜0.01)respectively and the ratios of Cyclin D1 and Bcl-2 protein expression were 2.37 and 3.81(P＜0.01),respectively.NK-4 inhibited the cell proliferation and induced apoptosis in a dose-and time-dependent manner and caused significant downregulation of Cychn D1 and Bcl-2.Conclusions The results show that overexpression of c-Met may play a critical role in the proliferation of VSMCs after bal- loon angioplasty.Selective c-Met inhibitor NK-4 may inhibit the proliferation and induce apoptosis of VSMCs through decreasing expression of Cyclin D1 and Bcl-2,indicating that C-Met inhibitor may be a new candidate for prevention of restenosis after angioplasty.