Selective estrogen receptor modulators: different actions on vascular cell adhesion molecule-1 (VCAM-1) expression in human endothelial cells.

Selective estrogen receptors modulators (SERMs) are a series of new compounds exerting estrogenic or anti-estrogenic effects in different tissues. 17Beta-estradiol is known to inhibit endothelial vascular cell adhesion molecule (VCAM)-1 expression. We studied the relative effects of the raloxifene analogue LY117018 and of tamoxifen on lipopolysaccharide (LPS)-induced VCAM-1 expression in cultured human saphenous vein endothelial cells (HSVEC) and on HSVEC adhesiveness towards U937 monocytoid cells. We here demonstrate a concentration-dependent inhibitory action on VCAM-1 protein expression both for 17beta-estradiol and LY117018. The action of both compounds was blocked by the pure anti-estrogen ICI 182,780. LY117018 did not antagonize 17beta-estradiol activity. On the contrary, tamoxifen had no effects of his own. Both 17beta-estradiol and LY117018 inhibited HSVEC VCAM-1 expression at the mRNA level, while tamoxifen was ineffective. Finally, 17beta-estradiol and LY117018, but not tamoxifen, inhibited HSVEC adhesiveness towards U937 monocytoid cells induced by LPS stimulation. Therefore, only some SERMs have potential anti-atherogenic actions exerted directly at the vascular level through the regulation of endothelial cell adhesion molecules expression and of endothelial-leukocyte interactions.