Effects of 17 beta-estradiol and progesterone on growth-factor-induced proliferation and migration in human female aortic smooth muscle cells in vitro

Objective: The significantly low prevalence of atherosclerotic cardiovascular disease in premenopausal women has been noted, and postmenopausal hormone replacement therapy (HRT) is associated with protection from this disease. The aim of this study was to investigate the effects of estrogen and progestin on growth-factor-induced vascular smooth muscle cell (VSMC) proliferation and migration in vitro. Methods: Two cell lines of human female aortic smooth muscle cells (AOSMCs) were used for the study. DNA synthesis was evaluated by [H-3]thymidine incorporation into cells. Migration assay was performed using modified Boyden chambers. Results: The presence of estrogen receptors was determined by Western and Northern blot analyses. [H-3]Thymidine incorporation into AOSMCs was induced by 10 ng/ml EGF alone, the combination of 10 ng/ml EGF with 2 ng/ml b-FGF-induced and 1 nM PDGF-BB alone. Migration of AOSMCs was induced by PDGF-BB. Since 17 beta-estradiol (E(2), 10(-9) M similar to 10(-6) M) inhibited the [H-3]thymidine incorporation into AOSMCs stimulated by above mitogens and the 1 nM PDGF-BB-induced AOSMC migration in a dose-dependent manner, estrone (E(1)), estriol (E(3)) and progesterone (P) had no significant effects. The combination of P (10(-9) M similar to 10(-6) M) did not show any effect on these inhibitory effects of 10(-7) M E(2). Preincubation of AOSMCs with the anti-estrogenic agent, tamoxifen (10(-6) M), significantly antagonized these inhibitory effects of 10(-7) M E(2). Conclusions: These findings suggest that the inhibitory effect of E(2) on VSMC proliferation and migration might be one of the factors involved in the decreased incidence of atherosclerotic cardiovascular disease in premenopausal women and postmenopausal HRT, and P might not affect these estrogenic responses.