Connecting Sex to Platelet Function after Mechanical Activation

心血管疾病是全球最常见的死亡原因。差异在于 心血管疾病在男性和女性中都得到了很好的证实，但尽管 血栓形成在缺血性中风、缺血性心脏病和静脉疾病中的重要性 血栓栓塞症、血小板功能的性别差异往往不在谈话中。 尽管如此，男性和女性在出血风险、抗血小板反应等方面存在差异 治疗、血栓相关疾病的发生率和结果，以及创伤后的死亡率。在……里面 结合荷尔蒙和遗传因素，差异可能是由于血小板的变异性。 生物学，如公认的血小板计数差异，据称表达的差异 关键表面受体，以及表面受体激活的可变性。虽然以前的工作已经 使用临床测试来检查男性和女性之间血栓形成功能的差异 发现轻微的显著差异或没有显著差异，这些测试使用经典的 生物化学激动剂激活血小板，而不是生物物理激活 机械受体血小板糖蛋白Ibα(GPIBα)和整合素αIIbβ3。在这项工作中，我试图 研究性别如何影响机械激活的血小板功能，这在动脉中是至关重要的 血栓形成。这项资助的目的是确定止血功能是否因性别而异。 在动脉、高切激活环境下，没有外源生化激动剂。这就做 还讨论了与动脉相关的血小板生物学方面是否存在性别差异 血栓形成，包括血小板机械受体GPIBα和整合素的机械激活 αIIbβ3、血小板流动粘附力和血小板收缩力。这项调查很重要 因为了解男性和女性之间血栓形成的差异性将影响 健康血小板功能的表征，未来研究的设计，抗血小板药物的应用 血小板治疗，以及未来预防和治疗疗法的发展。

Cardiovascular disease is the most common cause of death worldwide. Differences in cardiovascular disease in males and females have been well established, but despite the importance of thrombosis in ischemic stroke, ischemic heart disease, and venous thromboembolism, sex differences in platelet function are often absent from the conversation. None the less, males and females have differences in bleeding risk, response to anti-platelet therapy, thrombosis-related disease incidence and outcomes, and mortality post-trauma. In combination with hormonal and genetic factors, differences may be due to variability in platelet biology such as well-established differences in platelet count, alleged differences in expression of key surface receptors, and variability of surface receptor activation. While previous work has used clinical tests to examine differences in thrombotic function between males and females and found modest significant differences or no significant differences, these tests use classic biochemical agonists to activate platelets, rather than biophysical activation of the mechanoreceptors platelet glycoprotein Ibα (GPIbα) and integrin αIIbβ3. In this work, I seek to investigate how sex affects mechanically-activated platelet function, which is critical in arterial thrombosis. The goal of this grant is to determine whether hemostatic function varies by sex under arterial, high-shear activated environments without exogenous biochemical agonists. I will also address whether sex differences exist in aspects of platelet biology related to arterial thrombosis, including mechanical activatability of platelet mechanoreceptors GPIbα and integrin αIIbβ3, platelet adhesion in flow, and platelet contractile forces. This investigation is important because understanding variability in thrombosis between males and females will affect characterization of healthy platelet function, design of future research studies, application of anti- platelet treatments, and development of future preventative and curative therapeutics.