Estrogen induces proliferation and cell cycle specific apoptosis of synthetic vascular smooth muscle cells

Objective To investigate the effect of 17β-estradiol (E_2) on proliferation and apoptosis of vascular smooth muscle cells (VSMC) and the possible underlying mechanisms.Methods The progression of cell cycle,the apoptosis and the expressions of CyclinD1,bcl-2 and bax proteins were examined by flow cytometry in subcultured rat VSMC exposed to different concentrations (0-100 nmol/L) of 17β-estradiol.The intracellular localization of bax in VSMC was detected by using immunofluorescent cytochemistry and confocal laser scanning fluorescence microscopy.Results 17β-estradiol (1-100 nmol/L) promoted VSMC proliferation by accelerating their cell cycle progression from G1 to S phases (the rates of the VSMC at S phase were significantly increased,while those at G0/G1 decreased).This was accompanied by an up-regulation of CyclinD1 expression.At the same time,E_2 selectively increased the rate of apoptosis of the cells at G2/M phases in a time-and dose-dependant manner,which was accompanied by a significant raise of bax expression and the ratio of bax/bcl-2.The bax was located in the cytoplasm.Conclusion The effects of E_2 on subcultured (synthetic) VSMC are multiple:it promotes VSMC proliferation by enhancing the expression of CyclinD1 that accelerates G1 to S phase transition,and on the other hand,it induces apoptosis of the cells at G2/M phase by up-regulating the expression of bax.