ADVANCED GLYCOSYLATION END-PRODUCTS INDUCED TISSUE FACTOR EXPRESSION IN HUMAN MONOCYTE-LIKE U937 CELLS AND INCREASED TISSUE FACTOR EXPRESSION IN MONOCYTES FROM DIABETIC-PATIENTS

Tissue factor (TF) plays a central role in the initial activation of t he 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 w ere assessed by flow cytometric analysis. Human macrophage-like U937 c ells, which were shown to contain mRNA encoding the receptors of advan ced glycosylation end products (RAGE), expressed TF in a dose-dependen t manner on incubation with AGE-albumin. AGE-albumin-induced TF expres sion was completely inhibited by the anti-oxidant agents, catalase and probucol. TF expression in peripheral monocytes from normal volunteer s was also increased by AGE-albumin. Finally, TF expression in monocyt es 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-indu ced TF expression in macrophages/monocytes is mediated by oxidant stre ss. AGEs may promote thrombosis and the development of atherosclerosis by inducing TF expression in monocytes in patients with diabetes mell itus. (C) 1998 Elsevier Science Ireland Ltd.