Estrogen inhibits vascular smooth muscle cell-dependent adventitial fibroblast migration in vitro

Background-Mounting experimental evidence suggests that estrogen treatment protects against neointima formation in response to vascular injury in vivo , Previous studies have suggested that this process includes the activation and migration of adventitial fibroblasts. The present in vitro study was d esigned to establish a mechanism whereby estrogen attenuates migration of a dventitial fibroblasts. Methods and Results-Primary cultures of vascular smooth muscle cells (VSMCs ) and adventitial fibroblasts were derived from female Sprague-Dawley rats. Reverse transcriptase-polymerase chain reaction and Western blotting were used to determine that expression of the estrogen receptor (ER) was restric ted to early-passage VSMCs, Migration of transduced (retrovirally mediated) fibroblasts was determined by counting the number of blue lacZ-expressing cells attached to Boyden-type chambers preconditioned under defined experim ental conditions. Compared with growth medium alone, chambers treated with medium conditioned by VSMCs demonstrated a 2-fold increase in fibroblast mi gration, suggesting that VSMCs release soluble factor(s) competent to bind the Transwell membrane and promote fibroblast migration, In contrast, treat ment of VSMCs with 17 beta-estradiol (10(-9) to 10(-7) mol/L) before precon ditioning of the chamber induced a dose-dependent inhibition of fibroblast migration. Cotreatment of VSMCs with 17 beta-estradiol and the ER antagonis t ICI-182780 (10(-7) mol/L) blocked the inhibitory effect of estrogen on fi broblast migration. Conclusions-These observations suggest a novel mechanism of hormonal vasopr otection by which estrogen directly modulates VSMC expression of factor(s) controlling migration of adventitial fibroblasts via an ER-dependent mechan ism.