## 3 P2Y12 and Thrombis  
Thrombus caused by the abnormal activation of platelets is the pathological basis for the formation of many diseases. Under various physiological and pathological conditions, platelets can be activated and undergo processes such as adhesion, deformation, aggregation, particle release and synthesis of thromboxane A2, which ultimately leads to physiological hemostasis or pathological thrombosis [28]. Platelet activation participates in the injury repair response during vascular injury, which is very important for the physiological hemostasis process. Furthermore, in the process of damage repair, platelets are activated in blood vessels and will indirectly adhere to subendothelial collagen through von Willebrand factor (vWF) [29; 30]. Meanwhile, the platelet surface membrane glycoproteins GPVI and GPIa/IIa are also activated and directly adhere to collagen. However, under pathological conditions, when the blood flow shear rate is high, the GPIb/IX/V-vWF-collagen axis plays a key role in mediating the initial unstable platelet adhesion process, which is important for Ib/IX/V-vWF-collagen. Blocking of the axis is a key target for blocking platelet adhesion and subsequent reactions [31; 32; 33]. Among them, ARC-1779, as a nucleic acid aptamer of vWF, can block vWF and GPIb/IX/V by binding to the A1 region of vWF [34]. At the same time, abnormal platelet activation also causes arterial thrombosis to cause blood vessel stenosis or occlusion, resulting in ischemia of the body tissue or interruption of blood supply, which ultimately leads to the pathological basis of arterial thrombotic diseases such as coronary heart disease, acute coronary syndrome, stroke, sticky platelet syndrome, etc. [18; 35; 36]. The following protein-coupled receptorsare important receptors on the surface of platelets: thrombin receptors, PAR1, PAR3 and PAR4; ADP receptors, P2Y1 and P2Y12; prostaglandin receptors, such as thromboxane, prostacyclin, PDG2 and PGE2 receptors; and some lipid and chemokine receptors [37; 38]. ADP is the earliest and most important substance in the body that induces platelet aggregation. ADP exists in high-density granules in platelet cells, and is released when platelets undergo an aggregation reaction. In sticky platelet syndrome, due to the increased aggregation of ADP and epinephrine, a variety of unexplained thromboembolic diseases result [39]. Human platelets have two ADP receptors: the Gq-coupled P2Y1 and Gi-coupled P2Y12 receptors. Among them, P2Y1 receptor is distributed on platelets and other tissue cells. P2Y12 receptors are mainly distributed on platelets and glial cells and have been most studied on platelets. ADP released from damaged blood vessels and red blood cells in the in vivo environment mediates platelet aggregation by acting on the two G-protein coupled receptor subtypes 2 and 3. Platelet surface ADP receptors mainly include P2Y1 and P2Y12. P2Y1 is a Gq protein coupled receptor, and P2Y12 is a Gi protein coupled receptor (Figure 1). When the ADP activates the P2Y1 receptor, it increases the intracellular free Ca2+ and changes the platelet morphology, causing reversible aggregation. After ADP activates the P2Y12 receptor, the initial platelet aggregation induced by the P2Y12 receptor can cause the release of dense particles in the platelets (including a large amount of ADP), inhibit adenylate cyclase and trigger irreversible platelet aggregation [40; 41]. The P2Y1 receptor can only cause weak platelet activation, while P2Y12 can gradually amplify the signal. At the same time, the number of P2Y12 receptors on platelet membranes far exceeds that of P2Y1, so P2Y12 receptors have become one of the important targets of antiplatelet drugs [42]. P2Y12 receptor-mediated platelet activation is mainly achieved through the following mechanisms:  
1.