The Multifaceted Role of Platelets in Atherosclerosis and Ischemic Disease: Pathogenesis, Inflammation, and Therapeutic Opportunities

(1) Background: Atherosclerosis is a complex chronic inflammatory disease characterized by the plaque-induced thickening of medium-sized and large arterial walls. Chronic inflammation, lipid accumulation, and endothelial dysfunction play a critical role in pathophysiology of atherosclerosis. Along with immune cells, vascular smooth muscle cells, endothelial cells, and platelets play a critical role in the pathogenesis of atherosclerosis. Targeting platelet-related molecular mechanisms has emerged as a promising therapeutic strategy in treating atherosclerosis. However, potential targets are not clearly understood. This review discusses the multifaceted role of platelets in the pathogenesis of atherosclerosis and ischemic disease followed by the potential of targeting platelets. (2) Methods: Articles related to the role of platelets in atherosclerosis and underlying molecular mechanisms were searched from PubMed and Google Scholar using search terms atherosclerosis, platelets, therapeutics, targets; alone or in combination; (3) Results: Current research suggest that platelet-related molecular mechanisms play a critical role in plaque development, progression, and rupture. The mediators involved may serve as therapeutic targets; (4) Conclusions: Targeting platelets can attenuate atherosclerosis by interfering with platelet functions beyond blood clotting, such as promoting vascular inflammation and platelet adhesion.