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Originally published in Science Express on 18 November 2004
Science 10 December 2004:
Vol. 306. no. 5703, pp. 1954 - 1957
DOI: 10.1126/science.1103333
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Reports

COX-2-Derived Prostacyclin Confers Atheroprotection on Female Mice

Karine M. Egan,1 John A. Lawson,1 Susanne Fries,1 Beverley Koller,2 Daniel J. Rader,1 Emer M. Smyth,1 Garret A. FitzGerald1*

Female gender affords relative protection from cardiovascular disease until the menopause. We report that estrogen acts on estrogen receptor subtype alpha to up-regulate the production of atheroprotective prostacyclin, PGI2, by activation of cyclooxygenase 2 (COX-2). This mechanism restrained both oxidant stress and platelet activation that contribute to atherogenesis in female mice. Deletion of the PGI2 receptor removed the atheroprotective effect of estrogen in ovariectomized female mice. This suggests that chronic treatment of patients with selective inhibitors of COX-2 could undermine protection from cardiovascular disease in premenopausal females.

1 The Institute for Translational Medicine and Therapeutics, University of Pennsylvania, PA 19104, USA.
2 Department of Medicine, University of North Carolina, NC 27599, USA.

* To whom correspondence should be addressed. E-mail: garret{at}spirit.gcrc.upenn.edu

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