Estrogen stimulates delayed mitogen-activated protein kinase activity in human endothelial cells via an autocrine loop that involves basic fibroblast growth factor

Seunghee Kim-Schulze*, William L. Lowe, H. William Schnaper

*Corresponding author for this work

Research output: Contribution to journalArticle

43 Scopus citations

Abstract

Background-Estrogen plays a significant role in protecting premenopausal women from cardiovascular disease. We have found that estradiol augments endothelial cell activities related to vascular healing and that human coronary artery and umbilical vein endothelial cells express estrogen receptors (ERs). Classically, the ER functions as a transcription factor, but the cytoplasmic targets of this genomic effect have not been defined for endothelial cells. In the present study, we examined the potential role of the mitogen-activated protein (MAP) kinases ERK1 and ERK2 as mediators of estrogen action. Methods and Results-Human umbilical vein endothelial cells were estrogen depleted by culturing in hormone-free medium for 48 hours before experiments. 17β-Estradiol (E2) stimulated a delayed (3 hours) 5- to 7-fold induction of ERK1/2 activity requiring activation of ER and new transcription/translation. Conditioned media from cells stimulated for 3 hours with E2 induced immediate ERK1/2 activation and phosphorylation of the basic fibroblast growth factor (bFGF) receptor. Moreover, ERK1/2 activation by E2 or by conditioned media was abrogated by treatment with neutralizing anti-bFGF antibody. Conclusions-These data describe an autocrine mechanism for E2 induction of ERK1/2 in HUVEC. Because our previous studies suggested that certain cardioprotective effects of estrogen are genomic in nature, the results are consistent with the hypothesis that autocrine stimulation of endothelial ERK1/2 activity by bFGF may play a role in the beneficial effects of estrogen on cardiovascular biology.

Original languageEnglish (US)
Pages (from-to)413-421
Number of pages9
JournalCirculation
Volume98
Issue number5
DOIs
StatePublished - Aug 4 1998

Keywords

  • Endothelium
  • Fibroblast growth factor, basic
  • P 42 (MAP K) kinase
  • Signal transduction

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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