University Hospital and Rudolf Virchow Center, DFG-Research Center for Experimental Biomedicine, University of Würzburg, Josef-Schneider-Str. 2, 97080 Würzburg, Germany.
Trends Pharmacol Sci. 2012 Nov;33(11):583-90. doi: 10.1016/j.tips.2012.07.004. Epub 2012 Aug 15.
Platelet activation is a key step in the pathogenesis of ischemic cardio- and cerebrovascular diseases, which represent the leading causes of death and severe disability worldwide. Although existing antiplatelet drugs have proved beneficial in the clinic, their use is limited by their inherent effect on primary hemostasis, making the identification of novel pharmacological targets for platelet inhibition an important goal of cardiovascular research. In recent years, the central activating platelet collagen receptor, glycoprotein (GP) VI, has emerged as a promising antithrombotic target because its blockade or antibody-mediated depletion in circulating platelets was shown to effectively inhibit experimental thrombosis and thromboinflammatory disease states, such as stroke, without affecting hemostatic plug formation. In this review, we summarize the most important recent developments in understanding of GPVI function in hemostasis and thrombotic/inflammatory diseases and discuss the potential use of anti-GPVI agents to treat these pathologies in humans.
血小板激活是缺血性心脑血管疾病发病机制中的关键步骤,这些疾病是全球范围内导致死亡和严重残疾的主要原因。尽管现有的抗血小板药物已被证明在临床上有益,但它们的使用受到其对原发性止血的固有影响的限制,因此,寻找新的血小板抑制药理学靶点是心血管研究的一个重要目标。近年来,血小板胶原受体糖蛋白 (GP) VI 作为一种有前途的抗血栓靶点脱颖而出,因为阻断或抗体介导的循环血小板耗竭被证明可有效抑制实验性血栓形成和血栓炎症性疾病状态,如中风,而不会影响止血栓的形成。在这篇综述中,我们总结了在理解 GPVI 在止血和血栓炎症性疾病中的功能方面的最重要的最新进展,并讨论了使用抗-GPVI 药物治疗这些疾病的潜在用途。