Vol. 282, Issue 4, E746-E751, April 2002
High glucose abolishes the antiproliferative effect of
17
-estradiol in human vascular smooth muscle cells
Shanhong
Ling1,
Peter J.
Little2,
Maro R. I.
Williams1,
Aozhi
Dai1,
Kazuhiko
Hashimura1,
Jun-Ping
Liu3,
Paul A.
Komesaroff1,*, and
Krishnankutty
Sudhir1,*
1 Hormones and the Vasculature Laboratory, 2 Cell
Biology of Diabetes Laboratory, and 3 Molecular Signaling
Laboratory, Baker Medical Research Institute, Melbourne, Victoria 8008, Australia
We examined effects of
17
-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)- inhibitor,
LY-379196 (30 nmol/l). Western blotting showed that
PKC-1 protein increased in cells exposed to high
glucose, whereas PKC-
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- inhibitor LY-379196. Thus high glucose enhances human VSMC
proliferation and attenuates the antiproliferative effect of
E2 in VSMC via activation of PKC-.
high glucose; estrogen; proliferation; smooth muscle cells; protein
kinase C-
*
K. Sudhir and P. A. Komesaroff have contributed
equally to this study.
