Estradiol enhances endothelial cell interactions with extracellular matrix proteins via an increase in integrin expression and function.
Premenopausal women have a lower cardiovascular risk and a higher incidence of several autoimmune diseases involving blood vessels than men. Although the precise effects of estrogens on the cardiovascular system are largely unknown, recent data suggest that estrogens can exert direct regulatory effects on endothelial cells. In the present study, we show that 17beta-estradiol increases human umbilical vein endothelial cell attachment to the extracellular matrix proteins laminin-1, type IV collagen, type I collagen, and fibronectin. Estradiol enhanced adhesion most significantly to laminin-1 and to fibronectin-derived synthetic peptides containing an RGD sequence. Upon exposure to estradiol, an increase in beta1, alpha5 and alpha6 integrin mRNA was observed in subconfluent cells which was abrogated by treatment with cycloheximide. This increase was followed by a later enhancement in surface expression of the above integrins. In addition, integrin-mediated signaling was also enhanced by estrogens since an increase in tyrosine-phosphorylation of focal adhesion kinase induced by cell attachment was observed in estrogen-treated endothelial cells. Since integrins have an important role in mediating endothelial cell attachment, migration and differentiation, the increase in integrin expression and function induced by estradiol may be an important mechanism through which estrogens can promote neovascularization and vessel repair.