One of the earliest events in atherosclerosis is interaction of circulating mononuclear leukocytes and the endothelium. Endothelial cell (EC) activation by cytokines results in expression of adhesion molecules and production of chemotactic factors, augmenting leukocyte adhesion and recruitment, respectively. The incidence of atherosclerosis in premenopausal women is significantly less than that observed in age-matched males with similar risk profiles. Because estrogen has gene regulatory effects, we investigated whether 17β-estradiol (E2) can inhibit cytokine-mediated EC adhesion molecule transcriptional activation. Cultured human umbilical vein EC (estrogen receptor-positive) were propagated in gonadal hormone-free medium and were E2-pretreated for 48 hr before IL-1 activation. Detected by FACS® analysis, E2 strongly (60-80%) inhibited IL-1-mediated membrane E- selectin and vascular cell adhesion molecule-1 induction, and intercellular adhesion molecule-1 hyperinduction. 17α-estradiol (an inactive E2 stereoisomer) had no effect. This inhibition correlated with similar reductions in steady state-induced E-selectin mRNA levels, and was abrogated by the E2 antagonist ICI 164,384, demonstrating a specific, estrogen receptor-mediated effect. Nuclear runoffs confirmed suppression at the transcriptional level. The implications of these results for the cardiovascular protective role of estrogen are discussed.
|Number of pages||7|
|Journal||Journal of Clinical Investigation|
|Publication status||Published - Jul 1 1996|
- estrogen receptor
- gene regulation
- vascular endothelium
ASJC Scopus subject areas