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Fig. 1 | Thrombosis Journal

Fig. 1

From: Platelets and platelet adhesion molecules: novel mechanisms of thrombosis and anti-thrombotic therapies

Fig. 1

Current and novel antiplatlet therapies. Platelet adhesion to an injury site at a vessel wall is mediated by the exposure and binding of subendothelial matrix proteins (e.g. collagen, VWF, fibrinogen, and fibronectin) to glycoprotein (GP) receptors on the platelet surface. VWF binding to the GPIb-IX-V complex, collagen binding to platelet GPVI and integrin α2β1 receptors trigger a signal transduction process resulting in the local release of platelet activation agonists, such as thromboxane A2 and ADP. These agonists along with thrombin produced from coagulation cascades and activated platelets, bind to platelet surface bound G-coupled receptors inducing further platelet activation. Activation of platelet integrin αIIbβ3 induces platelet aggregation mediated by fibrinogen/VWF or the yet undetermined “X” ligands. Leukocyte-platelet adhesion can be driven by the interaction between platelet surface P-selectin and its counter-receptor PSGL-1 situated upon the leukocyte surface. Inhibition of platelet activation is mainly mediated by the PDE/PDE3 regulated degradation and PGI2, NO and GLP-1R regulated activation of cGMP or cAMP. Direct and indirect antithrombotic therapeutics are tabulated in the light colored boxes within the figure. The actions of antithrombotic therapies are depicted using red arrows, and some indirect antithrombotic agents (such as anti-atherosclerotic agents) are represented with purple arrows. Therapeutics, to name a few, listed in black, green, red and purple correspond to FDA-approved, phase III, phase II or preclinical development status, respectively. Numbered inhibitory arrows represent the actions of the correspondingly numbered therapies. Some other anti-platelet agents are not included, more information can be found in references 17, 18 and other publications. Abbreviations: COX-1 cyclooxygenase 1 GLP-1 glucagon-like peptide 1, GLP-1R glucagon-like peptide 1 receptor, PAR protease-activated receptor, PDE phosphodiesterase, PSGL-1 P-selectin glycoprotein ligand 1, TP thromboxane prostanoid receptor, TXA 2 thromboxane A2; VWF von Willebrand factor

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