Becker B F, Heindl B, Kupatt C, Zahler S
Dept. of Physiology, University of Munich, Germany.
Z Kardiol. 2000 Mar;89(3):160-7. doi: 10.1007/pl00007320.
The vascular endothelium influences not only the three classically interacting components of hemostasis: the vessel, the blood platelets and the clotting and fibrinolytic systems of plasma, but also the natural sequelae: inflammation and tissue repair. Two principal modes of endothelial behaviour may be differentiated, best defined as an anti- and a prothrombotic state. Under physiological conditions endothelium mediates vascular dilatation (formation of NO, PGI2, adenosine, hyperpolarizing factor), prevents platelet adhesion and activation (production of adenosine, NO and PGI2, removal of ADP), blocks thrombin formation (tissue factor pathway inhibitor, activation of protein C via thrombomodulin, activation of antithrombin III) and mitigates fibrin deposition (t- and scuplasminogen activator production). Adhesion and transmigration of inflammatory leukocytes are attenuated, e.g. by NO and IL-10, and oxygen radicals are efficiently scavenged (urate, NO, glutathione, SOD). When the endothelium is physically disrupted or functionally perturbed by postischemic reperfusion, acute and chronic inflammation, atherosclerosis, diabetes and chronic arterial hypertension, then completely opposing actions pertain. This prothrombotic, proinflammatory state is characterised by vaso-constriction, platelet and leukocyte activation and adhesion (externalization, expression and upregulation of von Willebrand factor, platelet activating factor, P-selectin, ICAM-1, IL-8, MCP-1, TNF alpha, etc.), promotion of thrombin formation, coagulation and fibrin deposition at the vascular wall (expression of tissue factor, PAI-1, phosphatidyl serine, etc.) and, in platelet-leukocyte coaggregates, additional inflammatory interactions via attachment of platelet CD40-ligand to endothelial, monocyte and B-cell CD40. Since thrombin formation and inflammatory stimulation set the stage for later tissue repair, complete abolition of such endothelial responses cannot be the goal of clinical interventions aimed at limiting procoagulatory, prothrombotic actions of a dysfunctional vascular endothelium.
血管、血小板以及血浆中的凝血和纤维蛋白溶解系统，还影响其自然后果：炎症和组织修复。内皮细胞行为主要有两种模式，最好定义为抗血栓形成状态和促血栓形成状态。在生理条件下，内皮介导血管舒张（生成一氧化氮、前列环素、腺苷、超极化因子），防止血小板黏附和激活（生成腺苷、一氧化氮和前列环素，清除二磷酸腺苷），阻断凝血酶形成（组织因子途径抑制剂，通过血栓调节蛋白激活蛋白C，激活抗凝血酶III）并减轻纤维蛋白沉积（生成组织型和尿激酶型纤溶酶原激活剂）。炎症白细胞的黏附和迁移会减弱，例如通过一氧化氮和白细胞介素-10，并且氧自由基会被有效清除（尿酸盐、一氧化氮、谷胱甘肽、超氧化物歧化酶）。当内皮因缺血后再灌注、急慢性炎症、动脉粥样硬化、糖尿病和慢性动脉高血压而受到物理破坏或功能扰动时，则会出现完全相反的作用。这种促血栓形成、促炎状态的特征是血管收缩、血小板和白细胞激活及黏附（血管性血友病因子、血小板活化因子、P选择素、细胞间黏附分子-1、白细胞介素-8、单核细胞趋化蛋白-1、肿瘤坏死因子α等的外化、表达和上调），促进血管壁处凝血酶形成、凝血和纤维蛋白沉积（组织因子、纤溶酶原激活物抑制剂-1、磷脂酰丝氨酸等的表达），并且在血小板-白细胞共聚体中，通过血小板CD40配体与内皮、单核细胞和B细胞CD40的结合产生额外的炎症相互作用。由于凝血酶形成和炎症刺激为后期组织修复奠定了基础，因此完全消除此类内皮反应不可能成为旨在限制功能失调的血管内皮的促凝、促血栓形成作用的临床干预目标。
