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Chronic estradiol treatment reduces platelet responses and protects mice from thromboembolism through the hematopoietic estrogen receptor α.

Abstract : Although estrogens are known to have a deleterious effect on the venous thrombosis risk and a preventive action on the development of arterial atheroma, their effect on platelet function in vivo remains unclear. Here, we demonstrate that a chronic high physiologic level of estradiol (E2) in mice leads to a marked decrease in platelet responsiveness ex vivo and in vivo compared with ovariectomized controls. E2 treatment led to increased bleeding time and a resistance to thromboembolism. Hematopoietic chimera mice harboring a selective deletion of estrogen receptors (ERs) α or β were used to demonstrate that the effects of E2 were exclusively because of hematopoietic ERα. Within ERα the activation function-1 domain was not required for resistance to thromboembolism, as was previously shown for atheroprotection. This domain is mandatory for E2-mediated reproductive function and suggests that this role is controlled independently. Differential proteomics indicated that E2 treatment modulated the expression of platelet proteins including β1 tubulin and a few other proteins that may impact platelet production and activation. Overall, these data demonstrate a previously unrecognized role for E2 in regulating the platelet proteome and platelet function, and point to new potential antithrombotic and vasculoprotective therapeutic strategies.
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https://www.hal.inserm.fr/inserm-00732474
Contributor : Marie Francoise Simon <>
Submitted on : Friday, September 14, 2012 - 4:52:20 PM
Last modification on : Tuesday, March 17, 2020 - 12:26:02 PM

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Marie-Cécile Valéra, Marie-Pierre Gratacap, Pierre Gourdy, Françoise Lenfant, Cendrine Cabou, et al.. Chronic estradiol treatment reduces platelet responses and protects mice from thromboembolism through the hematopoietic estrogen receptor α.. Blood, American Society of Hematology, 2012, 120 (8), pp.1703-12. ⟨10.1182/blood-2012-01-405498⟩. ⟨inserm-00732474⟩

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