Platelet-endothelial cell-cell interactions at the onset of atherosclerosis: mechanisms and implications

Platelets are primarily known for their roles in hemostasis and thrombosis; however, accumulating evidence highlights their significant contribution to endothelial dysfunction and the development of atherosclerosis. Upon adhering to the endothelium, platelets engage in reciprocal activation through a variety of membrane receptors and adhesion molecules, initiating inflammatory and immune responses that drive early atherogenic processes. Several studies have shown that platelet receptors traditionally associated with hemostasis also mediate adhesion to endothelial cells. In addition, recent research has uncovered novel molecular players and mechanisms involved in platelet tethering to the endothelium. This review explores the mechanisms underlying endothelial–platelet interactions during the early stages of atherosclerosis. We examine how platelet adhesion to endothelial cells contributes to the formation of atherosclerotic plaques and discuss potential therapeutic strategies aimed at disrupting these pro-atherogenic interactions. In particular, we discuss emerging anti-platelet agents that selectively target receptors involved in platelet–endothelial cell interactions, offering promising translational approaches to prevent or slow the onset of atherosclerosis.