Estrogen, heat shock proteins, and NFκB in human vascular endothelium

Karyn L. Hamilton, F. N. Mbai, S. Gupta, Anne A Knowlton

Research output: Contribution to journalArticlepeer-review

32 Scopus citations


Background-We hypothesized that estrogen would increase HSP72 in human coronary artery endothelial cells (HCAEC), and that these would be more sensitive to estrogen than our previous observations in myocytes. Methods and Results-HCAEC were treated with 17β-estradiol or tamoxifen, ranging from physiological to pharmacological(1 nM to 10 μmol/L) for either 24 hours (early) or 7 days (chronic). HSP expression was assessed by Western blots. Both early and chronic 17β-estradiol and tamoxifen increased HSP72. Electromobility shift assays (EMSA) showed activation of HSF-1 with early, but not chronic, 17β-estradiol. 17β-Estradiol activated NFκB within 10 minutes, and the ER-α selective inhibitor, ICI 182 780, abolished this effect. Transcription factor decoys containing the heat shock element blocked HSP72 induction. Estrogen pretreatment decreased lactate dehydrogenase release with hypoxia. This protective effect persisted despite blockade of HSF-1 by decoys. However, an NF-κB decoy prevented the increase in HSP72 and abolished the estrogen-associated protection during hypoxia. Conclusions-17β-Estradiol upregulates HSP72 early and chronically via different mechanisms in HCAEC, and provides cytoprotection during hypoxia, independent of HSP72 induction. NF-κB mediates the early increase in HSP72, suggesting that estrogen activates NF-κB via a nongenomic, receptor-dependent mechanism, and this leads to activation of HSF-1. Activation of NF-κB was critical for estrogen-associated protection. Further studies are needed to elucidate the involved signaling pathways.

Original languageEnglish (US)
Pages (from-to)1628-1633
Number of pages6
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Issue number9
StatePublished - Sep 2004


  • Endothelium
  • Estrogen
  • HSP72
  • Hypoxia
  • Signal transduction

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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