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Figure 8 Schematic representation of the mechanism that stabilizes platelets at the edge of a growing thrombus exposed to elevated shear rates. (A) Circulating platelets adhere and become activated onto collagen through multiple adhesive interactions, initiated by glycoprotein (GP) Ib binding to von Willebrand factor (VWF) under high shear rate conditions. Full activation depends on released adenosine diphosphate (ADP) and leads to the binding of soluble adhesive ligands such as VWF and fibrinogen. These form the new substrate for the recruitment of circulating platelets, again initiated under high shear rate conditions by GP Ib-VWF binding. Adhesive interactions and soluble agonists present in the environment of the growing thrombus lead to activation of the newly recruited platelets and further ADP release. (B) Cyclic Ca2+ signaling induced by released ADP and mediated by P2Y1 and P2Y12 maintains GP IIb/IIIa activation necessary for the sustained binding of adhesive molecules and stability of the aggregate. The first layer of platelets interacting with the collagen surface may not require sustained ADP stimulation for stable adhesion.
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