PLATELET ADHESION ON ARTERIAL SUBENDOTHELIUM

血小板粘附于血管内皮下是血小板活化的关键初始步骤。 主要止血。 本项目采用了灌注技术， Baumgartner到动脉段，以更好地定义 血小板和内皮下。 在最初的研究中， 血小板和单克隆抗体研究表明，血小板 血小板膜糖蛋白IIb/IIIa（GPIIb/IIIa）对血小板膜功能的影响 沿着内皮下表面扩散。 随后的研究 证明了血管性血友病因子（vWf）的碳水化合物部分是 这对蛋白质支持血小板粘附的能力很重要。 接下来， 我们发现动脉粥样硬化的动脉内皮下大约 形成血栓的程度只有正常表面的一半 热消融 动脉粥样硬化斑块与催化热尖端导管或 Erbium-YAG激光引起表面反应性的显著降低， 血小板，而光化学消融斑块与激发激光 导致血小板粘附与未治疗的 斑块 最后，arg-gly-asp-肽和来自Y链的肽 纤维蛋白原被证明在一定剂量下抑制血小板粘附， 依赖的方式。 这表明GP IIb/IIIa粘附蛋白 纤维蛋白原、纤维蛋白原和血管性血友病因子的结合位点 与血小板的相互作用在血小板粘附中是重要的。 许多 已经定义了改变血小板粘附的单克隆抗体 与内皮下表面接触。

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 (GPIIb/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 exciter 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.