A Critical Role of Platelet Adhesion in the Initiation of Atherosclerotic Lesion Formation

TLDR

The contribution of platelets to the process of atherosclerosis remains unclear. Platelets adhere to carotid endothelium before atherosclerotic lesions, involving GP Ibα and GPIIb‑IIIa, coincide with inflammatory gene expression, precede leukocyte invasion, and blockade of adhesion markedly reduces leukocyte accumulation and attenuates lesion formation in multiple arterial sites, establishing platelets as a major initiator of atherogenesis.

Abstract

The contribution of platelets to the process of atherosclerosis remains unclear. Here, we show in vivo that platelets adhere to the vascular endothelium of the carotid artery in ApoE−/− mice before the development of manifest atherosclerotic lesions. Platelet–endothelial cell interaction involved both platelet glycoprotein (GP)Ibα and GPIIb-IIIa. Platelet adhesion to the endothelium coincides with inflammatory gene expression and preceded atherosclerotic plaque invasion by leukocytes. Prolonged blockade of platelet adhesion in ApoE−/− mice profoundly reduced leukocyte accumulation in the arterial intima and attenuated atherosclerotic lesion formation in the carotid artery bifurcation, the aortic sinus, and the coronary arteries. These findings establish the platelet as a major player in initiation of the atherogenetic process.