Diabetic erythrocytes bearing advanced glycation end products induce vascular dysfunctions

Abstract

Vascular dysfunction is one of the major complications in diabetes mellitus. The extended interaction of proteins with aldoses results in non enzymatic glycation, ultimately leading to formation of Advanced Glycation End Products (AGEs). We previously showed that increased adhesion of diabetic red blood cells (RBCs) was statistically correlated with the vascular severity and the glycated hemoglobin level. We demonstrated that diabetic erythrocytes bear cell surface AGE which enhance their binding to endothelium, resulting in oxidative stress through generation of thiobarbituric acid reactive substances (TBARS) and activation of the transcription factor NFKB, both of which were prevented by preincubating of endothelial cells with anti-RAGE IgG or the antioxidant probucol. Incubation of diabetic erythrocytes with endothelial cells increased the diffusional transit of ¹²⁵I albumin, an effect prevented by preincubation of endothelial cells with anti-RAGE antibodies or an antioxidant compound. These data indicate that the interaction of diabetic erythrocytes with endothelium results in oxidative stress one consequence of which is increased vascular permeability.