PLATELET ADHESION ON ARTERIAL SUBENDOTHELIUM

血小板与血管内皮下细胞的黏附是 一次止血。该项目采用了灌流技术。 Baumgartner对动脉节段之间的相互作用进行更好的定义 血小板和内皮下层。在最初的工作中，格兰兹曼的血栓减少症 血小板和单抗研究表明，血小板 膜糖蛋白IIb/IIIa(GP IIb/IIIa)对血小板的重要作用 沿着内皮下表面扩散。随后的研究证明 Von Willebrand因子(VWF)的碳水化合物部分对 这种蛋白质支持血小板黏附的能力。接下来，我们展示了 动脉粥样硬化性血管内皮下细胞约为 血栓形成为正常表面。动脉粥样硬化的热消融治疗 用催化热端导管或Er-YAG激光治疗斑块 导致对血小板的表面反应性显著降低，而 准分子激光光化学消融斑块形成血小板 粘连与未经处理的斑块上观察到的粘连难以区分。 最后，精氨酸-甘氨酸-天冬氨酸多肽和纤维蛋白原Y链上的一种多肽 均被证明能抑制血小板黏附，呈剂量依赖关系 时尚。这表明GP IIb/IIIa黏附蛋白结合位点 参与纤维蛋白原、纤维蛋白原和von Willebrand因子的相互作用 与血小板的结合对血小板的粘附性很重要。众多的单克隆性 已经定义了抗体来改变血小板与细胞的粘附性 内皮下表面。

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.