Vascular Medicine, University Hospital Würzburg and Rudolf Virchow Center, DFG Research Center for Experimental Biomedicine, University of Würzburg, Würzburg, Germany.
J Thromb Haemost. 2011 Jul;9 Suppl 1:92-104. doi: 10.1111/j.1538-7836.2011.04361.x.
Platelet adhesion, activation and aggregation on the exposed subendothelial extracellular matrix (ECM) are essential for haemostasis, but may also lead to occlusion of diseased vessels. Binding of the glycoprotein (GP)Ib-V-IX complex to immobilised von Willebrand factor (VWF) initiates adhesion of flowing platelets to the ECM, and thereby enables the collagen receptor GPVI to interact with its ligand and to mediate platelet activation. This process is reinforced by locally produced thrombin and platelet-derived secondary mediators, such as adenosine diphosphate (ADP) and thromboxane A(2) (TxA(2)). Together, these events promote a shift of β1 and β3 integrins from a low to a high affinity state for their ligands through 'inside-out' signalling allowing firm platelet adhesion and aggregation. Formed platelet aggregates are stabilised by fibrin formation and signalling events between adjacent platelets involving multiple platelet receptors, such as the newly discovered C-type lectin-like receptor 2 (CLEC-2). While occlusive thrombus formation is the principal pathogenic event in myocardial infarction, the situation is more complex in ischaemic stroke where infarct development often progresses despite sustained early reperfusion of previously occluded major intracranial arteries, a process referred to as 'reperfusion injury'. Increasing experimental evidence now suggests that early platelet adhesion and activation events, orchestrate a 'thrombo-inflammatory' cascade in this setting, whereas platelet aggregation and thrombus formation are not required. This review summarises recent developments in understanding the principal platelet adhesion receptor systems with a focus on their involvement in arterial thrombosis and ischaemic stroke models.
血小板在暴露的内皮下细胞外基质（ECM）上的黏附、激活和聚集对于止血至关重要，但也可能导致病变血管阻塞。糖蛋白（GP）Ib-V-IX 复合物与固定化的血管性血友病因子（VWF）结合，启动流动血小板与 ECM 的黏附，从而使胶原受体 GPVI 与其配体相互作用并介导血小板激活。这一过程得到局部产生的凝血酶和血小板衍生的二级介质（如二磷酸腺苷（ADP）和血栓烷 A（2）（TxA（2）））的加强。这些事件共同促使β1和β3整联蛋白通过“内-外”信号从低亲和力状态转变为高亲和力状态，允许血小板牢固黏附和聚集。形成的血小板聚集体通过纤维蛋白形成和相邻血小板之间涉及多种血小板受体（如新发现的 C 型凝集素样受体 2（CLEC-2））的信号事件得到稳定。虽然闭塞性血栓形成是心肌梗死的主要致病事件，但在缺血性中风中情况更为复杂，尽管先前阻塞的颅内大血管持续早期再灌注，但梗死发展通常仍会进展，这一过程称为“再灌注损伤”。越来越多的实验证据表明，早期血小板黏附和激活事件在这种情况下协调“血栓-炎症”级联反应，而血小板聚集和血栓形成并非必需。本综述总结了理解主要血小板黏附受体系统的最新进展，重点介绍其在动脉血栓形成和缺血性中风模型中的作用。
