Estrogen accelerates G1 to S phase transition and induces a G2/M phase-predominant apoptosis in synthetic vascular smooth muscle cells

Abstract

Objective To investigate the mechanisms underlying the vascular-protective effects of estrogen. Methods The synthetic (subcultured for 3–4 passages) rat vascular smooth muscle cells were exposed to gradient concentrations (10 − 10 –10 − 5 M) of 17β-estradiol. The growth, cell cycle progression and apoptosis of the cells, and the related proteins including Cyclin D1, Cdk4, p38, Bax and Bcl-2 were analyzed in MTT, flow cytometry, ELISA or Western blot. Results 17β-estradiol in the physiological concentrations (10 − 10 –10 − 8 M) promoted the smooth muscle cell growth in a concentration-dependent manner, accelerated transition of the cells from G1 to S phases, and up-regulated expressions of Cyclin D1 and Cdk4. Meanwhile, the hormone (10 − 9 –10 − 7 M) triggered a G2/M phase-predominant apoptosis of the cells in a concentration- and time-dependent manner, which was accompanied by increased phosphorylation of p38 and expression of Bax. Conclusions The effect of estrogen on the synthetic vascular smooth muscle cell is dual. It promotes proliferation of the cells by accelerating their G1/S phase transition via up-regulating Cyclin D1 and Cdk4; and on the other hand, it induces apoptosis of the proliferating cells by up-regulating Bax through p38-MAPK pathway.