Estradiol enhances endothelial cell interactions with extracellular matrix proteins via an increase in integrin expression and function

Maria C. Cid, Jordi Esparza, H. William Schnaper, Manel Juan, Jordi Yague, Derrick S. Grant, Alvaro Urbano-Márquez, Gary S. Hoffman, Hynda K. Kleinman*

*Corresponding author for this work

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

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 17β-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 β1, α5 and α6 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.

Original languageEnglish (US)
Pages (from-to)271-280
Number of pages10
JournalAngiogenesis
Volume3
Issue number3
DOIs
StatePublished - Jan 1 1999

Keywords

  • Endothelial cell
  • Estrogen
  • Integrins

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cancer Research

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    Cid, M. C., Esparza, J., Schnaper, H. W., Juan, M., Yague, J., Grant, D. S., Urbano-Márquez, A., Hoffman, G. S., & Kleinman, H. K. (1999). Estradiol enhances endothelial cell interactions with extracellular matrix proteins via an increase in integrin expression and function. Angiogenesis, 3(3), 271-280. https://doi.org/10.1023/A:1009023329294