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Science 306 (5703): 1954-1957

Copyright © 2004 by the American Association for the Advancement of Science

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*

Abstract: 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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