From the Department of Experimental Biomedicine, University Hospital Würzburg and Rudolf Virchow Center for Experimental Biomedicine, University of Würzburg, Würzburg, Germany.
Arterioscler Thromb Vasc Biol. 2014 Aug;34(8):1615-20. doi: 10.1161/ATVBAHA.114.303408. Epub 2014 Jun 12.
Coronary artery thrombosis and ischemic stroke are often initiated by the disruption of an atherosclerotic plaque and consequent intravascular platelet activation. Thus, antiplatelet drugs are central in the treatment and prevention of the initial, and subsequent, vascular events. However, novel pharmacological targets for platelet inhibition remain an important goal of cardiovascular research because of the negative effect of existing antiplatelet drugs on primary hemostasis. One promising target is the platelet collagen receptor glycoprotein VI. Blockade or antibody-mediated depletion of this receptor in circulating platelets is beneficial in experimental models of thrombosis and thrombo-inflammatory diseases, such as stroke, without impairing hemostasis. In this review, we summarize the importance of glycoprotein VI and (hem)immunoreceptor tyrosine-based activation motif signaling in hemostasis, thrombosis, and thrombo-inflammatory processes and discuss the targeting strategies currently under development for inhibiting glycoprotein VI and its signaling.
冠状动脉血栓形成和缺血性中风通常由动脉粥样硬化斑块破裂和随之发生的血管内血小板激活引起。因此，抗血小板药物是治疗和预防初始和随后血管事件的核心。然而，由于现有抗血小板药物对原发性止血有负面影响，血小板抑制的新的药理学靶点仍然是心血管研究的一个重要目标。一个有前途的靶点是血小板胶原受体糖蛋白 VI。在血栓形成和血栓炎症性疾病（如中风）的实验模型中，阻断或抗体介导的该受体在循环血小板中的耗竭可带来益处，而不会损害止血功能。在这篇综述中，我们总结了糖蛋白 VI 及其（半）免疫受体酪氨酸激活基序信号在止血、血栓形成和血栓炎症过程中的重要性，并讨论了目前正在开发的抑制糖蛋白 VI 及其信号的靶向策略。
