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(Circulation Research. 2005;97:415.)
© 2005 American Heart Association, Inc.

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Effects of Estrogen Replacement Therapies on Mouse Platelet Function and Glycoprotein VI Levels

Xing-Hong Leng, Wei Zhang, Bernhard Nieswandt, Paul F. Bray

From Medicine/Thrombosis Research (X.-H.L., W.Z., P.F.B.), Baylor College of Medicine, Houston, Tex; and Vascular Biology (B.N.), Rudolf Virchow Center for Experimental Biomedicine, University of Würzburg, Germany.

Correspondence to Paul F. Bray, MD, Thrombosis Research Section, Baylor College of Medicine, One Baylor Plaza, BCM 286, N1319, Houston, TX 77030. E-mail pbray{at}bcm.tmc.edu

Clinical trials have shown estrogen replacement therapy (ERT) is associated with adverse arterial vascular events. Arterial thrombosis is initiated by platelet activation, but the in vivo effects of estrogens on platelet function are not well understood. We used a murine model of menopause to examine 3 major ERT regimes and test the hypothesis that ERT affects the intrinsic platelet response to agonists. The 3 ERT regimes studied were: (1) oral conjugated equine estrogen (CEE), (2) oral 17-ß estradiol (E2), and (3) subcutaneously implanted E2 (SQ E2). Paired ovariectomized littermates were treated with these regimes or placebo for 21 days. Two platelet agonists, thrombin and the GPVI-specific agonist collagen-related peptide (COL-RP), were used to evaluate platelet reactivity. Among the 3 regimens, (1) oral CEE enhanced platelet reactivity to COL-RP, (2) oral E2 had no effect on platelet reactivity to COL-RP and (3) SQ E2 increased platelet sensitivity to thrombin but lowered reactivity to COL-RP. Thus, the in vivo effects of estrogen on platelet function are agonist specific and dependent on hormone formulation and mode of delivery. The GPVI collagen receptor likely mediated some of these effects, because the ERT regimens induced changes in platelet surface GPVI expression corresponding to the observed platelet activation.

Key Words: estrogen • glycoprotein VI • hormone replacement therapy • platelets

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