Endothelial function and hemostasis
Endothelial function and hemostasis
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DOI：
10.1007/s003920050461
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发表时间：
2000-03-01
期刊：
影响因子：
--
通讯作者：
Zahler, S
中科院分区：
文献类型：
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作者：
Becker, BF;Heindl, B;Zahler, S
血管内皮不仅影响止血的三个经典相互作用的成分：血管、血小板以及血浆的凝血和纤溶系统，而且还影响自然后遗症：炎症和组织修复。内皮行为的两种主要模式可能有所不同，最好定义为抗血栓状态和促血栓状态。在生理条件下，内皮介导血管扩张（形成 NO、PGI(2)、腺苷、超极化因子），防止血小板粘附和激活（产生腺苷、NO 和 PGI(2)，去除 ADP），阻止凝血酶形成（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（t-和 scu-纤溶酶原激活剂的产生）。炎症白细胞的粘附和迁移减弱，例如通过NO和IL-10，有效清除氧自由基（尿酸盐、NO、谷胱甘肽、SOD）。当内皮因缺血后再灌注、急性和慢性炎症、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乱时，就会发生完全相反的作用。这种促血栓形成、促炎状态的特征是血管收缩、血小板和白细胞活化和粘附（血管性血友病因子、血小板活化因子、P-选择素、ICAM-1、IL-8、MCP-1、TNF α等的外化、表达和上调），促进凝血酶形成、凝血和血管壁上的纤维蛋白沉积（表达 组织因子、PAI-1、磷脂酰丝氨酸等），并且在血小板-白细胞共聚集中，通过血小板 CD40 配体与内皮细胞、单核细胞和 B 细胞 CD40 的附着而产生额外的炎症相互作用。由于凝血酶的形成和炎症刺激为以后的组织修复奠定了基础，因此完全消除这种内皮反应不能成为旨在限制功能失调的血管内皮的促凝血、促血栓形成作用的临床干预的目标。
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, PGI(2), adenosine, hyperpolarising factor), prevents platelet adhesion and activation (production of adenosine, NO and PGI(2), 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 scu-plasminogen 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 (externalisation, 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.