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

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.

Molecular and Functional Differences Induced in Thrombospondin-1 by the Single Nucleotide Polymorphism Associated with the Risk of Premature, Familial Myocardial Infarction

“…In view of the prominence of TSP-1 in platelets, the dominant role of these cells in thrombus formation leading to MI (27), and recent studies implicating platelets in the development of atherosclerotic lesions (28,29), we focused on the influence of TSP-1 on platelet aggregation. Low dose (5 M) ADP was used as both a model and a physiologically relevant agonist to stimulate a submaximal aggregation response (ϳ35% of maximum) of platelets in plasma.…”

Novel uses for anti‐platelet agents as anti‐inflammatory drugs

“…However, interactions between platelets and inflammatory cells take place during atherosclerosis and this stimulation of an inflammatory response within the atherosclerotic plaque may trigger acute coronary events via reactive oxygen species (ROS) production and MMP secretion (Poubelle and Borgeat, 2002). Substantial clinical evidence demonstrates activation of circulating platelets in diseases with a substantial inflammatory component acting on the vasculature, for example, acute coronary syndromes such as myocardial infarction and unstable angina (Sarma et al, 2002) and atherosclerosis (Massberg et al, 2002). These studies suggest a participation of platelets in the inflammatory responses as well as the recognized events leading to thrombus formation.…”

Augmented atherogenesis in ApoE-null mice co-exposed to polychlorinated biphenyls and 2,3,7,8-tetrachlorodibenzo-p-dioxin

“…Emerging data suggest that platelet activation plays a pivotal role in early atherosclerotic lesion formation (Massberg et al, 2002;Li, 2013). PF4 is synthesized in megakaryocytes and stored in α-granules.…”