High glucose blocks the effects of estradiol on human vascular cell growth: Differential interaction with estradiol and raloxifene

Dalia Somjen, Channing J. Paller, Batya Gayer, Fortune Kohen, Esther Knoll, Naftali Stern

Research output: Contribution to journalArticlepeer-review

Abstract

Because diabetic women appear not to be protected by estrogen in terms of propensity to cardiovascular disease, we tested the possibility that chronic hyperglycemia modulates the effects of E2 on vascular cell growth in vitro. Human endothelial cells (E304) and vascular smooth muscle cells (VSMC) were grown in normal glucose (5.5mmol/l), high glucose (22mmol/l) or high manitol (22nmol/l; an osmotic control) for 7 days. In endothelial cells glucose per se stimulated DNA synthesis. However E2- (but not RAL-) stimulated [3H] thymidine incorporation was attenuated in the presence of high glucose. In parallel, E2-dependent MAP-kinase-kinase activity was blocked in the presence of high glucose. High glucose increased basal creatine kinase (CK) specific activity, but E 2-stimulated CK was not significantly impaired in the presence of high glucose. In VSMC, high glucose prevented the inhibitory effect of high E2 (but not of high RAL) concentrations on DNA synthesis. High glucose also prevented E2-induced MAP-kinase-kinase activity. In contrast, while high glucose augmented basal CK, the relative E 2-induced changes were roughly equal in normal and high high glucose media. Hence, high glucose blocks several effects of E2 on vascular cell growth, which are mediated, in part, via the MAP-kinase system and are likely contributors to E2's anti-atherosclerotic properties. Since RAL's estrogen-mimetic effects on human vascular cell growth were independent of MAP-kinase activation and were not affected by hyperglycemia, the potential use of RAL to circumvent the loss of estrogen function induced by hyperglycemia and diabetes in the human vasculature should be further explored.

Original languageEnglish (US)
Pages (from-to)101-110
Number of pages10
JournalJournal of Steroid Biochemistry and Molecular Biology
Volume88
Issue number1
DOIs
StatePublished - Jan 2004

Keywords

  • Creatine kinase
  • Endothelial cells
  • Glucose
  • MAP-kinase
  • MAP-kinase-kinase
  • Vascular smooth muscle cells

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Endocrinology
  • Clinical Biochemistry
  • Cell Biology

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