Platelet receptor signaling in thrombus formation |
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Authors: | David Stegner Bernhard Nieswandt |
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Institution: | 1.Chair of Vascular Medicine, University Hospital and Rudolf Virchow Center, DFG Research Center for Experimental Biomedicine,University of Würzburg,Würzburg,Germany |
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Abstract: | Platelet activation and subsequent thrombus formation at sites of vascular injury is crucial for normal hemostasis, but it
can also cause myocardial infarction and stroke. The initial capture of flowing platelets to the injured vessel wall is mediated
by the interaction of the glycoprotein (GP) Ib-V-IX complex with von Willebrand factor immobilized on the exposed subendothelial
extracellular matrix. Tethered platelets are then able to bind to collagens through the immunoglobulin-like receptor GPVI
and to initiate cellular activation, a process that is reinforced by G protein-coupled receptors stimulated by locally produced
thrombin and soluble mediators released from activated platelets. These signaling events lead to a rise in the cytosolic Ca2+ concentration, rearrangement of the cytoskeleton, release of granule content, and functional upregulation of integrin adhesion
receptors allowing firm adhesion and thrombus growth. Fully activated platelets also undergo a procoagulant conversion thereby
facilitating coagulation and thrombus stabilization. This review summarizes the most important receptor systems and signaling
mechanisms involved in platelet activation and thrombus formation with special focus on recent discoveries. |
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