Levin E G, Hanano M
Department of Molecular and Experimental Medicine, Scripps Clinic and Research Foundation.
Nihon Rinsho. 1992 Feb;50(2):303-6.
Procoagulant, anticoagulant, and fibrinolytic activities are associated with endothelial cells and involve the production, secretion, and receptor mediated binding of proteins involved in these processes. The procoagulant aspect of endothelial cells function involves the production and release of von Willebrand Factor(vWF), the production of tissue factor, and the presence of Factor IX/IXa receptors on the cell surface. Secretion of vWf will promote the initial steps in thrombus formation by supporting platelet-platelet interaction and platelet-subendothelial matrix adhesion. Tissue factor which is undetectable in resting cells appears after exposure to various cytokines and initiates factor VIIa activation of factors IX and X. Receptors of Factor IX/IXa are also present and mediate the assembly of the prothrombinase complex on the endothelial cell surface. The anticoagulant pathway involves the cell surface protein thrombomodulin, protein C and its cofactor protein S. Thrombomodulin binds thrombin which activates protein C which in the presence of protein S cleaves and inactivates Factors V and VIII. Inactivation of these two coagulation cofactors halts the coagulation. Finally, endothelial cells also play a pivotal role in the fibrinolytic system. Production and regulated secretion of tissue plasminogen activator creates a profibrinolytic state in the endothelial cell environment. In addition, receptors for plasminogen and urokinase are also present, constituting a cell surface mediated fibrinolytic pathway. Plasminogen activator inhibitor type I, the primary inhibitor of tPA, is also produced by endothelial cells. Thus endothelial cells can promote and inhibit fibrinolysis, depending on the prevailing environmental conditions.
促凝、抗凝和纤溶活性与内皮细胞相关,涉及这些过程中相关蛋白质的产生、分泌以及受体介导的结合。内皮细胞功能的促凝方面涉及血管性血友病因子(vWF)的产生和释放、组织因子的产生以及细胞表面因子IX/IXa受体的存在。vWf的分泌通过支持血小板-血小板相互作用和血小板-内皮下基质黏附来促进血栓形成的初始步骤。在静息细胞中无法检测到的组织因子,在暴露于各种细胞因子后出现,并启动因子VIIa对因子IX和X的激活。因子IX/IXa的受体也存在,并介导凝血酶原酶复合物在内皮细胞表面的组装。抗凝途径涉及细胞表面蛋白血栓调节蛋白、蛋白C及其辅因子蛋白S。血栓调节蛋白结合凝血酶,凝血酶激活蛋白C,蛋白C在蛋白S存在的情况下裂解并使因子V和VIII失活。这两种凝血辅因子的失活会使凝血停止。最后,内皮细胞在纤溶系统中也起着关键作用。组织型纤溶酶原激活物的产生和调节分泌在内皮细胞环境中创造了一种促纤溶状态。此外,纤溶酶原和尿激酶的受体也存在,构成了一种细胞表面介导的纤溶途径。内皮细胞还产生I型纤溶酶原激活物抑制剂,它是tPA的主要抑制剂。因此,内皮细胞可以根据当时的环境条件促进和抑制纤溶。