Progesterone regulates proliferation of endothelial cells

Citation
F. Vazquez et al., Progesterone regulates proliferation of endothelial cells, J BIOL CHEM, 274(4), 1999, pp. 2185-2192
Citations number
52
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biochemistry & Biophysics
Journal title
JOURNAL OF BIOLOGICAL CHEMISTRY
ISSN journal
0021-9258 → ACNP
Volume
274
Issue
4
Year of publication
1999
Pages
2185 - 2192
Database
ISI
SICI code
0021-9258(19990122)274:4<2185:PRPOEC>2.0.ZU;2-A
Abstract
The use of steroid hormones in postmenopausal replacement therapy has been associated with prevention of cardiovascular disease. Although the contribu tion of estradiol to endothelial cell function has been addressed, little i nformation is available on the effect of progestins on this cell type. Here , we provide direct evidence for the presence of functional nuclear progest erone receptor in endothelial cells and demonstrate that physiological leve ls of progesterone inhibit proliferation through a nuclear receptor-mediate d mechanism. The effects of progesterone were blocked by pretreatment with a progesterone receptor antagonist, and progesterone receptor-deficient end othelial cells failed to respond to the hormone. We evaluated the effect of progesterone by analysis of aorta re-endothelialization experiments in wil d-type and progesterone receptor knockout mice. The rate of re-endotheliali zation was significantly decreased in wild-type mice when in the presence o f progesterone, whereas there was no difference between control and progest erone-treated progesterone receptor knockout mice. FACS analysis showed tha t progestins arrest endothelial cell cycle in G(1). The lag in cell cycle p rogression involved reduction in cyclin-dependent kinase activity, as shown by down-regulation in retinoblastoma protein phosphorylation. In addition, treatment of endothelial cells with progestins altered the expression of c yclin E and A in accordance with G(1) arrest. These results have important implications to our current knowledge of the effect of steroids on endothel ial cell function and to the overall contribution of progesterone to vascul ar repair.