PLATELET ADHESION ON ARTERIAL SUBENDOTHELIUM

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Platelet adhesion to vascular subendothelium is a crucial initial step in primary hemostasis. This project applies the perfusion technique of Baumgartner to arterial segments to better define the interaction between platelets and subendothelium. In initial work, Glanzmann's thrombasthenia platelets and monoclonal antibody studies demonstrated that platelet membrane glycoprotein IIb/IIIa (GP IIb/IIIa) was important for platelet spreading along the subendothelial surface. Subsequent studies demonstrated that carbohydrate moieties of von Willebrand factor (vWf) are important for the protein's ability to support platelet adherence. Next, we showed that atherosclerotic arterial subendothelium was approximately half as thrombogenic as the normal surface. Thermal ablation of atherosclerotic plaque with either a catalytic hot-tipped catheter or an erbium-YAG laser caused a profound reduction in surface reactivity toward platelets, whereas photochemical ablation of plaque with an excimer laser led to platelet adherence indistinguishable from that observed on untreated plaque. Finally, arg-gly-asp-peptides and a peptide from the Y chain of fibrinogen were demonstrated to inhibit platelet adherence in a dose-dependent fashion. This indicates that the GP IIb/IIIa adhesive protein binding site involved in fibrinogen, fibrinogen and von Willebrand factor interactions with platelets is important in platelet adherence. Numerous monoclonal antibodies have been defined which modify the platelet adhesion with the subendothelial surface.