DIABETIC ERYTHROCYTES BEARING ADVANCED GLYCATION END-PRODUCTS INDUCE VASCULAR DYSFUNCTIONS

Vascular dysfunction is one of the major complications in diabetes mel litus. The extended interaction of proteins with aldoses results in no n enzymatic glycation, ultimately leading to formation of Advanced Gly cation End products (AGEs). We previously showed that increased adhesi on of diabetic red blood cells (RBCs) was statistically correlated wit h the vascular severity and the glycated hemoglobin level. We demonstr ated that diabetic erythrocytes bear cell surface AGE which enhance th eir binding to endothelium, resulting in oxidative stress through gene ration of thiobarbituric acid reactive substances (TBARS) and activati on of the transcription factor HFKB, both of which were prevented by p reincubating of endothelial cells with anti-RAGE Ige or the antioxidan t probucol. Incubation of diabetic erythrocytes with endothelial cells increased the diffusional transit I albumin, an effect prevented by p reincubation of endothelial cells with anti-RAGE antibodies or an anti oxidant compound. These data indicate that the interaction of diabetic erythrocytes with endothelium results in oxidative stress one consequ ence of which is increased vascular permeability. Copyright (C) 1996 E lsevier Science Ltd