Increase in antithrombotic function vascular endothelium antithrombin-III

正常血管内皮细胞优先产生前列腺素12和血栓调节蛋白等抗血栓因子，而不是组织因子等促血栓因子，从而阻止血栓的形成。然而，如果细胞受到血液中各种激动剂的刺激，细胞的平衡就会改变，从而减少抗血栓因子的产生，增加血栓前因子的产生，从而使血液变成血栓。抗凝血酶-III(AF-III)是一种凝血酶的生理性抑制剂，能刺激血管内皮细胞，诱导前列腺素I2的产生。本研究旨在评估AT-III除了诱导前列腺素I2.1的产生外，是否还能促进血管内皮细胞的各种抗血栓功能。培养的血管内皮细胞暴露于肿瘤坏死因子α后，通过上调组织因子的转录，诱导细胞膜表面组织因子的表达。结论：1.AT-Ⅲ可通过抑制TF基因转录来抑制肿瘤坏死因子α诱导的TF表达。内皮细胞经抗癌药物博莱霉素刺激后，通过上调ELAM-1的转录，诱导细胞表面ELAM-1的表达。AT-III预处理不能阻止博莱霉素诱导的ELAM-1的表达。氧化低密度脂蛋白中的氧化磷脂降低血管内皮细胞RARs、RXRα和Sp1蛋白的表达。这些减少的蛋白质通过抑制TM基因的转录，诱导细胞表面血栓调节蛋白(TM)的表达。AT-III预处理不能阻止氧化型低密度脂蛋白诱导的TM下调。这些结果表明，AT-III可能通过抑制凝血酶和诱导前列腺素I2的产生而发挥抗血栓作用，但不能抑制博莱霉素诱导的ELAM-1的表达和氧化型低密度脂蛋白诱导的TM下调。

Normal vascular endothelial cells preferentially produce antithrombotic factors such as prostaglandin 12 and thrombomodulin than preduction of prothrombotic factors such as tissue factor, so that the cells are preventing thrombus formation. However, if the cells are stimulated by various agonists in the blood, the cells change balance to reduce production of antithrombomotic factors and increase production of prothrombotic factor, so that the blood was turned to form thrombus. Antithrombin-III(AF-III), which is a physiological inhibitor for thrombin, stimulates endothelial cells and induces production of prostaglandin I2. The present studies were undertaken to evaluate whether AT-III can promote various antithrombotic functions in endothelial cells other than the induced production of prostaglandin I2.1. When cultured vascular endothelial cells were exposed to TNFα, the cells induce tissue factor (TF) expression on the membrane surface of the cells through up-regulation of TF transcription. Pretreatment of the cells with At-III prevented TNFα-induced TF expression through depression of TF gene transcription.2. Expression of ELAM-1, which is a adhesion molecule for lenkocytes, was induced by exposure of endothelial cells to bleomycin, a anticancer drug, on the cell surface through up-regulation of ELAM-1 transcription. AT-III pretreatment did not prevent the bleomycin-induced ELAM-1 expression.3. Oxidized phospholipid in oxidized LDL reduced expression of RARs, RXRα and Sp1 proteins in endothelial cells. These reduced proteins induced thrombomodulin(TM) expression on the surface of the cells through suppression of transcription of TM gene. AT-III pretreatment did not prevent oxidized LDL-induced down-regulation of TM. These results suggested that AT-III can act as antithomotic agent through inhibition of thrombin and induction of prostaglandin I2 producion, but not the bleomycin-induced ELAM-1 expression and the oxidized LDL-induced TM down-regulation.