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血小板信号转导与疾病:血栓及其他相关疾病的靶向治疗。

Platelet Signaling and Disease: Targeted Therapy for Thrombosis and Other Related Diseases.

机构信息

Departments of Pharmacology (J.Y., W.L., M.H.) and Internal Medicine, Division of Cardiovascular Medicine (M.H.), University of Michigan, Ann Arbor, Michigan.

Departments of Pharmacology (J.Y., W.L., M.H.) and Internal Medicine, Division of Cardiovascular Medicine (M.H.), University of Michigan, Ann Arbor, Michigan

出版信息

Pharmacol Rev. 2018 Jul;70(3):526-548. doi: 10.1124/pr.117.014530.

Abstract

Platelets are essential for clotting in the blood and maintenance of normal hemostasis. Under pathologic conditions such as atherosclerosis, vascular injury often results in hyperactive platelet activation, resulting in occlusive thrombus formation, myocardial infarction, and stroke. Recent work in the field has elucidated a number of platelet functions unique from that of maintaining hemostasis, including regulation of tumor growth and metastasis, inflammation, infection, and immune response. Traditional therapeutic targets for inhibiting platelet activation have primarily been limited to cyclooxygenase-1, integrin , and the P2Y receptor. Recently identified signaling pathways regulating platelet function have made it possible to develop novel approaches for pharmacological intervention in the blood to limit platelet reactivity. In this review, we cover the newly discovered roles for platelets as well as their role in hemostasis and thrombosis. These new roles for platelets lend importance to the development of new therapies targeted to the platelet. Additionally, we highlight the promising receptor and enzymatic targets that may further decrease platelet activation and help to address the myriad of pathologic conditions now known to involve platelets without significant effects on hemostasis.

摘要

血小板对于血液的凝结和正常止血至关重要。在动脉粥样硬化等病理情况下,血管损伤通常会导致血小板过度激活,从而导致闭塞性血栓形成、心肌梗死和中风。该领域的最新研究阐明了一些与维持止血不同的血小板功能,包括调节肿瘤生长和转移、炎症、感染和免疫反应。抑制血小板激活的传统治疗靶点主要局限于环氧化酶-1、整合素和 P2Y 受体。最近发现的调节血小板功能的信号通路使得有可能开发新的药理学干预血液中血小板反应性的方法。在这篇综述中,我们介绍了血小板的新作用及其在止血和血栓形成中的作用。这些血小板的新作用使得开发针对血小板的新疗法变得重要。此外,我们还强调了有希望的受体和酶靶点,这些靶点可能进一步减少血小板激活,并有助于解决现在已知涉及血小板的多种病理情况,而不会对止血产生显著影响。

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