**2. Platelets and Atherothrombosis**

Platelets are anucleated cells (1.5–3.0 μm in diameter) that originate from the fragmentation of the cytoplasm of the megakaryocyte through endomitosis. This process leads to the formation of platelets that enter the bloodstream [32,33].

Platelets circulate as discoid-shaped elements. In response to vascular damage, they emit pseudopodia, secreting the content of their granules and remodeling their membrane [32]. They are formed by a plasma membrane expressing important glycoproteic receptors: collagen receptors (glycoprotein (GP) IIb/IIa, GPIb/IX, GPVI, GPIa/IIa, GPIV), and non-glycoproteic receptors: adenosine diphosphate (ADP) receptors (P2Y1, P2Y12), thrombin receptors (PAR1, PAR4), thromboxane A2 receptor (TxA2), serotonin receptor, and prostacyclin I2 receptor. The receptor–agonist interaction participates in the outside/inside or inside/outside platelet signaling leading to platelet activation and/or inhibition [32,34].

Platelets, in their functional aspects, involve the processes of adhesion, activation, secretion, and platelet aggregation (Figure 1). Adhesion occurs in response to vascular damage; platelet membrane receptors interact with their respective ligands and bind to the injured wall resulting in platelets' morphological changes and secretion of their alpha and dense granule content [35]. Then, platelets begin the aggregation process which is characterized by platelet–platelet binding to form a platelet aggregate. Their functionality can be modified by CVRFs, e.g., developing a platelet hyperactivation state [36]. This condition has been

described as an increase in the capacity of activation, secretion, and aggregation against low concentrations of agonists, due to alterations in different signaling pathways [37,38].

**Figure 1.** Platelet function in the process of primary hemostasis. ADP, adenosine diphosphate; VWF, von Willebrand factor; GP, glycoprotein; 5HT: serotonin.

**Figure 2.** Participation of platelets in the atherothrombotic process. VWF, von Willebrand factor; GP, glycoprotein; IL, interleukin, PF4, platelet factor 4; PSGL-1, glycoprotein ligand-1 P-selectin; RANTES, beta-regulatory chemokine; VCAM-1, vascular cell-1 adhesion molecule.
