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

• Published in: American journal of physiology: endocrinology and metabolism 2002-04, Vol.282 (4), p.E746-E751
• Main Authors: Ling, Shanhong, Little, Peter J., Williams, Maro R. I., Dai, Aozhi, Hashimura, Kazuhiko, Liu, Jun-Ping, Komesaroff, Paul A., Sudhir, Krishnankutty
• Format: Article
• Language: English
• ISSN: 0193-1849; 1522-1555
• DOI: 10.1152/ajpendo.00111.2001

We examined effects of 17β-estradiol (E 2 ) 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-β 1 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, E 2 (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 E 2 were blocked by the estrogen receptor (ER) antagonist ICI-182780, indicating ER dependence. In high glucose, the inhibitory effect of E 2 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 E 2 in VSMC via activation of PKC-β.