Increase in antithrombotic function vascular endothelium antithrombin-III

正常的血管内皮细胞优先产生抗血栓形成因子如前列腺素12和血栓调节蛋白，而不是产生促血栓形成因子如组织因子，因此细胞防止血栓形成。然而，如果细胞被血液中的各种激动剂刺激，细胞改变平衡以减少抗血栓形成因子的产生并增加促血栓形成因子的产生，从而使血液转向形成血栓。抗凝血酶-III（AF-III）是凝血酶的生理抑制剂，刺激内皮细胞并诱导前列腺素I2的产生。本研究进行评估是否AT-III可以促进各种抗血栓功能的内皮细胞以外的前列腺素I2.1的诱导生产。当培养的血管内皮细胞暴露于TNFα时，细胞通过上调组织因子（TF）转录诱导细胞膜表面TF表达。用At-III预处理细胞可通过抑制TF基因的转录来阻止TNFα诱导的TF表达.通过将内皮细胞暴露于抗癌药物博来霉素，在细胞表面上通过上调ELAM-1转录来诱导ELAM-1的表达，ELAM-1是一种用于淋巴细胞的粘附分子。AT-III预处理不能阻止博莱霉素诱导的ELAM-1表达.氧化LDL中的氧化磷脂降低内皮细胞RAR、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上的血栓调节蛋白（TM）表达。AT-III预处理不能阻止氧化LDL诱导的TM下调。这些结果表明，AT-Ⅲ可通过抑制凝血酶和诱导前列腺素I2的产生而发挥抗炎作用，但不能抑制博莱霉素诱导的ELAM-1表达和氧化LDL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.