High glucose abolishes the antiproliferative effect of 17β-estradiol in human vascular smooth muscle cells

Shanhong Ling, Peter J. Little, Maro R I Williams, Aozhi Dai, Kazuhiko Hashimura, Jun Ping Liu, Paul A. Komesaroff, Krishnankutty Sudhir

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Abstract

We examined effects of 17β-estradiol (E2) on human vascular smooth muscle cell (VSMC) proliferation under normal (5 mmol/l) and high (25 mmol/l) glucose concentrations. Platelet-derived growth factor (PDGF) BB (20 ng/ml)-induced increases in DNA synthesis and proliferation were greater in high than normal glucose concentrations; the difference in DNA synthesis was abolished by a protein kinase C (PKC)-β inhibitor, LY-379196 (30 nmol/l). Western blotting showed that PKC-β1 protein increased in cells exposed to high glucose, whereas PKC-α protein and total PKC activity remained unchanged, compared with normal glucose cultures. In normal glucose, E2 (1-100 nmol/l) inhibited PDGF-induced DNA synthesis by 18-37% and cell proliferation by 16-22% in a concentration-dependent manner. The effects of E2 were blocked by the estrogen receptor (ER) antagonist ICI-182780, indicating ER dependence. In high glucose, the inhibitory effect of E2 on VSMC proliferation was abolished but was restored in the presence of the PKC-β inhibitor LY-379196. Thus high glucose enhances human VSMC proliferation and attenuates the antiproliferative effect of E2 in VSMC via activation of PKC-β.

Original languageEnglish
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume282
Issue number4 45-4
Publication statusPublished - 29 Jun 2002
Externally publishedYes

Keywords

  • Estrogen
  • High glucose
  • Proliferation
  • Protein kinase C-β
  • Smooth muscle cells

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