Hypothetical model of atherogenesis triggered by platelets. Activated platelets roll along the endothelial monolayer via GPIbα/P-selectin or PSGL-1/P-selectin. Thereafter, platelets firmly adhere to vascular endothelium via β₃ integrins, release proinflammatory compounds (IL-1β, CD40L), and induce a proatherogenic phenotype of ECs (chemotaxis, MCP-1; adhesion, ICAM-1). Subsequently, adherent platelets recruit circulating leukocytes, bind them, and inflame them by receptor interactions and paracrine pathways, thereby initiating leukocyte transmigration and foam cell formation. Thus, platelets provide the inflammatory basis for plaque formation before physically occluding the vessel by thrombosis upon plaque rupture.