Takeya H, Suzuki K
Department of Molecular Biology on Genetic Disease, Mie University School of Medicine, Tsu.
Rinsho Byori. 1994 Apr;42(4):333-9.
Recent advances in determining anti-thrombogenic functions of vascular endothelial cells are reviewed. The following anticoagulant and fibrinolytic systems of endothelial cells are physiologically important; (1) Endothelial cell-derived metabolites including prostacyclin and nitric oxide (NO) support platelet inactivity. (2) Antithrombin III and tissue factor pathway inhibitor (TFPI) bound to heparin-like proteoglycans on endothelial cell membrane inhibit activated serine protease coagulation factors such as thrombin, factor Xa and factor VIIa-tissue factor complex. (3) Thrombomodulin converts thrombin from procoagulant into anticoagulant. Thrombin associated to thrombomodulin on endothelial cells activates protein C. Activated protein C in concert with protein S bound to endothelial cell membrane inactivates factors Va and VIIIa. (4) A receptor for both tissue plasminogen activator and plasminogen on endothelial cells provides an efficient plasmin generating system. Perturbation of these anti-thrombogenic systems of endothelial cells is caused by endotoxin (LPS), cytokines such as interleukin-1 and tumor necrosis factor (TNF), and risk factors for atherogenesis including lipoprotein(a) and homocysteine may result in arterial or venous thrombosis with subsequent development of atherosclerosis.
本文综述了血管内皮细胞抗血栓形成功能研究的最新进展。内皮细胞的以下抗凝和纤溶系统具有重要生理意义:(1)内皮细胞衍生的代谢产物,如前列环素和一氧化氮(NO),可维持血小板的非活性状态。(2)抗凝血酶III和组织因子途径抑制剂(TFPI)与内皮细胞膜上的类肝素蛋白聚糖结合,可抑制活化的丝氨酸蛋白酶凝血因子,如凝血酶、因子Xa和因子VIIa-组织因子复合物。(3)血栓调节蛋白可将凝血酶由促凝剂转变为抗凝剂。与内皮细胞上血栓调节蛋白结合的凝血酶可激活蛋白C。活化的蛋白C与结合在内皮细胞膜上的蛋白S协同作用,使因子Va和VIIIa失活。(4)内皮细胞上组织型纤溶酶原激活剂和纤溶酶原的受体可形成高效的纤溶酶生成系统。内皮细胞这些抗血栓形成系统的紊乱是由内毒素(LPS)、细胞因子如白细胞介素-1和肿瘤坏死因子(TNF)引起的,而动脉粥样硬化的危险因素,如脂蛋白(a)和同型半胱氨酸,可能导致动脉或静脉血栓形成,随后发展为动脉粥样硬化。