Platelets and platelet adhesion molecules: novel mechanisms of thrombosis and anti-thrombotic therapies.
Platelets and platelet adhesion molecules: novel mechanisms of thrombosis and anti-thrombotic therapies.
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DOI：
10.1186/s12959-016-0100-6
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发表时间：
2016
影响因子：
3.1
通讯作者：
Ni H
中科院分区：
文献类型：
--
作者：
Xu XR;Carrim N;Neves MA;McKeown T;Stratton TW;Coelho RM;Lei X;Chen P;Xu J;Dai X;Li BX;Ni H
血小板是血栓形成和止血的中心介质。在血管损伤部位，血小板聚集（即粘附和聚集）构成第一波止血。由凝血级联启动的血液凝固是凝血酶产生的第二波，增强磷脂酰丝氨酸暴露，可以显着增强细胞凝血酶的产生并增强血液凝固。最近，血浆纤连蛋白和其他蛋白质在受损血管壁上的沉积已被确定为一种新的“止血蛋白质波”，发生在血小板聚集之前（即经典的第一波止血）。如果动脉粥样硬化斑块破裂，这三波止血可能会转化为致病性，并导致不受控制的血管闭塞和血栓性疾病（例如心脏病和中风）。目前的抗血小板疗法已显着降低了心血管死亡率，然而，治疗中的血栓事件、血小板减少症和出血并发症仍然是继续激励创新和推动治疗进步的主要问题。新的证据使血小板粘附分子重新成为人们关注的焦点，成为开发新型抗血栓药物的目标。这些潜在的抗血小板靶点主要包括血小板受体糖蛋白（GP）Ib-IX-V复合物、β3整合素（αIIb亚基和β3亚基的PSI结构域）和GPVI。为了在不影响止血的情况下平衡抑制血栓形成的功效，已经做出了许多努力。这篇小综述将更新血栓形成的机制和抗血小板治疗的现状，并将重点关注血小板粘附分子和针对它们的新型抗血栓治疗。
Platelets are central mediators of thrombosis and hemostasis. At the site of vascular injury, platelet accumulation (i.e. adhesion and aggregation) constitutes the first wave of hemostasis. Blood coagulation, initiated by the coagulation cascades, is the second wave of thrombin generation and enhance phosphatidylserine exposure, can markedly potentiate cell-based thrombin generation and enhance blood coagulation. Recently, deposition of plasma fibronectin and other proteins onto the injured vessel wall has been identified as a new “protein wave of hemostasis” that occurs prior to platelet accumulation (i.e. the classical first wave of hemostasis). These three waves of hemostasis, in the event of atherosclerotic plaque rupture, may turn pathogenic, and cause uncontrolled vessel occlusion and thrombotic disorders (e.g. heart attack and stroke). Current anti-platelet therapies have significantly reduced cardiovascular mortality, however, on-treatment thrombotic events, thrombocytopenia, and bleeding complications are still major concerns that continue to motivate innovation and drive therapeutic advances. Emerging evidence has brought platelet adhesion molecules back into the spotlight as targets for the development of novel anti-thrombotic agents. These potential antiplatelet targets mainly include the platelet receptors glycoprotein (GP) Ib-IX-V complex, β3 integrins (αIIb subunit and PSI domain of β3 subunit) and GPVI. Numerous efforts have been made aiming to balance the efficacy of inhibiting thrombosis without compromising hemostasis. This mini-review will update the mechanisms of thrombosis and the current state of antiplatelet therapies, and will focus on platelet adhesion molecules and the novel anti-thrombotic therapies that target them.