Effects of Estrogen Replacement Therapies on Mouse Platelet Function and Glycoprotein VI Levels
- 2 September 2005
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Circulation Research
- Vol. 97 (5), 415-417
- https://doi.org/10.1161/01.res.0000181025.43762.cf
Abstract
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-β 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.Keywords
This publication has 11 references indexed in Scilit:
- Transvaginal Ultrasound Measurement of Endometrial Thickness as a Biomarker for Estrogen ExposureCancer Epidemiology, Biomarkers & Prevention, 2004
- Platelet Receptor Glycoprotein VI-Mediated Adhesion to Type I Collagen Under Hydrodynamic FlowAnnals of Biomedical Engineering, 2004
- The WHI Estrogen-Alone Trial—Do Things Look Any Better?JAMA, 2004
- Role of platelets in coronary thrombosis and reperfusion of ischemic myocardiumCardiovascular Research, 2004
- Platelets of Female Mice Are Intrinsically More Sensitive to Agonists Than Are Platelets of MalesArteriosclerosis, Thrombosis, and Vascular Biology, 2004
- Platelet-collagen interaction: is GPVI the central receptor?Blood, 2003
- Effects of postmenopausal hormone replacement therapy on lipid, lipoprotein, and apolipoprotein (a) concentrations: analysis of studies published from 1974–2000Fertility and Sterility, 2001
- Analysis of the Roles of 14-3-3 in the Platelet Glycoprotein Ib-IX–Mediated Activation of Integrin αIIbβ3 Using a Reconstituted Mammalian Cell Expression ModelThe Journal of cell biology, 1999
- Cardioprotective effects of individual conjugated equine estrogens through their possible modulation of insulin resistance and oxidation of low-density lipoproteinFertility and Sterility, 1997
- THE MOUSE UTERINE WEIGHT METHOD FOR THE ASSAY OF ESTROGENS1Endocrinology, 1941