Certain Progestins Prevent the Enhancing Effect of 17 -Estradiol on NO-Mediated Inhibition of Platelet Aggregation by Endothelial Cells

نویسندگان

  • Murielle Zerr-Fouineau
  • Marie Jourdain
  • Caroline Boesch
  • Markus Hecker
  • Christian Bronner
  • Valérie B. Schini-Kerth
چکیده

Objectives—Estro-progestin treatments have been associated with an increased risk of thromboembolic events in postmenopausal women. This study examined whether progestins affect the stimulatory effect of estrogens on the endothelial formation of nitric oxide (NO), a potent antithrombotic factor. Methods and Results—Experiments were performed with human endothelial cells. Endothelial NO synthase (eNOS) and GTP cyclohydrolase I (GTPCH I) mRNA expression was assessed by RT-PCR, eNOS protein by Western blotting, NO formation by electron spin resonance spectroscopy, and platelet aggregation by an aggregometer. Medroxyprogesterone acetate (MPA), progesterone, levonorgestrel, and nomegestrol acetate prevented the 17 -estradiol (17 -E)–induced expression of eNOS mRNA and protein. MPA and progesterone reduced the 17 -E–induced formation of NO and potentiation of the inhibitory effect of endothelial cells on platelet aggregation whereas levonorgestrel and nomegestrol acetate were without effect. Moreover, MPA and progesterone prevented the 17 -E–induced expression of GTPCH I mRNA. Mifepristone, a glucocorticoid and progesterone receptor antagonist, and L-sepiapterin prevented the inhibitory effect of MPA and progesterone on platelet aggregation. Conclusions—Certain progestins, including MPA, attenuate the 17 -E–induced NO-mediated inhibition of platelet aggregation by endothelial cells through preventing both eNOS and GTPCH I expression most likely via activation of glucocorticoid receptors. (Arterioscler Thromb Vasc Biol. 2009;29:00-00.)

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Certain progestins prevent the enhancing effect of 17beta-estradiol on NO-mediated inhibition of platelet aggregation by endothelial cells.

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تاریخ انتشار 2008