Thus, G proteins are centrally involved in the second phase of platelet-dependent thrombus formation. ECM indicates extracellular matrix Fg, fibrinogen. These diffusible mediators then act on platelets nearby and recruit them into the growing platelet plug. Activation of these receptors strengthens the adhesion of the first and second layers of adhering platelets, induces platelet-shape change, and further drives the formation and release of mediators.
This results in the integrin-mediated adhesion of platelets and some cellular activation, which leads to the release and production of diffusible mediators such as ADP, TxA 2, and thrombin acting via GPCRs. The initial contact of platelets with the subendothelial extracellular matrix is mediated by vWF and GPIbα, followed by the activation of platelets by collagen via the collagen receptor GPVI. Activation of platelets at sites of vascular injury. Through the activation of G protein–mediated signaling pathways, they can further increase their own formation and release, thus acting as positive-feedback mediators that amplify the initial signals to ensure the rapid activation and recruitment of platelets into a growing thrombus ( Figure 1).įigure 1. These diffusible mediators have in common that they act via G protein–coupled receptors (GPCRs). These mediators include ADP/ATP and thromboxane A 2 (TxA 2), which are secreted or released from activated platelets and thrombin, which is produced on the surface of activated platelets. The recruitment of additional platelets is mediated by a variety of locally accumulating mediators that are produced or released once platelet adhesion has been initiated and some level of platelet activation through platelet adhesion receptors has occurred. 4,5 The interaction of activated integrins with the extracellular matrix then mediates the firm adhesion of platelets to the injured vessel wall, resulting in the formation of a platelet monolayer.ĭuring the next stage of platelet activation, a platelet plug forms through the recruitment of additional platelets from the circulation and their integrin α IIbβ 3-mediated aggregation (see Figure 1). GPVI is unable to mediate adhesion but, via activation of the FcRγ chain, induces intracellular signaling processes which promote the inside-out activation of integrins such as α IIbβ 3 (GPIIb/IIIa) or α 2β 1 (GPIa/IIa). 1,2 The initial interaction of platelets with the extracellular matrix under conditions of high sheer rates and the subsequent strengthening of this interaction involves the platelet vWF receptor GPIb/V/IX and the collagen receptor GPVI 2–4 (which will be covered in a forthcoming review in this series).
Platelet adhesion and activation at sites of vascular wall injury is initiated by a multistep process involving the interaction of platelets with the subendothelial extracellular matrix which contains adhesive macromolecules including collagen and von Willebrand factor (vWF).
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