Ichikawa K, Yoshinari M, Iwase M, Wakisaka M, Doi Y, Iino K, Yamamoto M, Fujishima M
Second Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Atherosclerosis. 1998 Feb;136(2):281-7. doi: 10.1016/s0021-9150(97)00221-9.
Tissue factor (TF) plays a central role in the initial activation of the extrinsic coagulation pathway and is thought to be involved in the development of atherosclerosis and thrombosis. The effect of advanced glycosylation end products (AGEs) on TF expression and its mechanism were assessed by flow cytometric analysis. Human macrophage-like U937 cells, which were shown to contain mRNA encoding the receptors of advanced glycosylation end products (RAGE), expressed TF in a dose-dependent manner on incubation with AGE-albumin. AGE-albumin-induced TF expression was completely inhibited by the anti-oxidant agents, catalase and probucol. TF expression in peripheral monocytes from normal volunteers was also increased by AGE-albumin. Finally, TF expression in monocytes from individuals with diabetes mellitus, in whom the concentration of circulating AGEs is reported to be increased, was higher than that in monocytes from normal controls. These results suggest that AGE-induced TF expression in macrophages/monocytes is mediated by oxidant stress. AGEs may promote thrombosis and the development of atherosclerosis by inducing TF expression in monocytes in patients with diabetes mellitus.
组织因子（TF）在外源性凝血途径的初始激活中起核心作用，并且被认为参与动脉粥样硬化和血栓形成的发展。通过流式细胞术分析评估了晚期糖基化终产物（AGEs）对TF表达的影响及其机制。已证明含有编码晚期糖基化终产物受体（RAGE）的mRNA的人巨噬细胞样U937细胞，在与AGE-白蛋白孵育时以剂量依赖性方式表达TF。抗氧化剂过氧化氢酶和普罗布考完全抑制了AGE-白蛋白诱导的TF表达。正常志愿者外周血单核细胞中的TF表达也因AGE-白蛋白而增加。最后，据报道循环AGEs浓度升高的糖尿病患者单核细胞中的TF表达高于正常对照者单核细胞中的TF表达。这些结果表明，AGE诱导的巨噬细胞/单核细胞中TF表达是由氧化应激介导的。AGEs可能通过诱导糖尿病患者单核细胞中的TF表达来促进血栓形成和动脉粥样硬化的发展。
