title: Platelet adhesion and activation mechanisms in arterial thrombosis and ischaemic stroke.
abstract: 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.
authors.affiliation: Vascular Medicine, University Hospital Würzburg and Rudolf Virchow Center, DFG Research Center for Experimental Biomedicine, University of Würzburg, Würzburg, Germany. bernhard.nieswandt@virchow.uni-wuerzburg.de
authors.forename: B
authors.initials: B
authors.lastname: Nieswandt
authors.forename: I
authors.initials: I
authors.lastname: Pleines
authors.forename: M
authors.initials: M
authors.lastname: Bender
mesh_terms: D001792:Blood Platelets / Q000166:cytology*; D002545:Brain Ischemia / Q000473:pathology*; D002448:Cell Adhesion; D006801:Humans; D015539:Platelet Activation; D013927:Thrombosis / Q000473:pathology*