Advanced glycation end products (AGEs) on the surface of diabetic erythrocytes bind to the vessel wall via a specific receptor inducing oxidant stress in the vasculature: A link between surface-associated AGEs and diabetic complications

J. L. Wautier, M. P. Wautier, A. M. Schmidt, G. M. Anderson, O. Hori, C. Zoukourian, L. Capron, O. Chappey, S. D. Yan, J. Brett, P. J. Guillausseau, David Stern

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Abstract

Vascular complications are an important cause of morbidity and mortality in patients with diabetes. The extent of vascular complications has been linked statistically to enhanced adherence of diabetic erythrocytes to endothelial cells (ECs) and to the accumulation of a class of glycated proteins termed advanced glycation end products (AGEs). We hypothesized that formation of AGEs on the surface of diabetic erythrocytes could mediate their interaction with ECs leading to binding and induction of vascular dysfunction. Enhanced binding of diabetic erythrocytes to ECs was blocked by preincubation of erythrocytes with anti-AGE IgG or preincubation of ECs with antibodies to the receptor for AGE (RAGE). Immunoblotting of cultured human ECs and immunostaining of normal/diabetic human tissue confirmed the presence of RAGE in the vessel wall. Binding of diabetic erythrocytes to endothelium generated an oxidant stress, as measured by production of thiobarbituric acid-reactive substances (TBARS) and activation of the transcription factor NF-κB, both of which were blocked by probucol or anti-RAGE IgG. Erythrocytes from diabetic rats infused into normal rats had an accelerated, early phase of clearance that was prevented, in part, by antibody to RAGE. Liver tissue from rats infused with diabetic erythrocytes showed elevated levels of TBARS, which was prevented by pretreatment with anti-RAGE IgG or probucol. Thus, erythrocyte surface AGEs can function as ligands that interact with RAGE on endothelium. The extensive contact of diabetic erythrocytes bearing surface- associated AGEs with vessel wall RAGE could be important in the development of vascular complications.

Original languageEnglish (US)
Pages (from-to)7742-7746
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume91
Issue number16
DOIs
StatePublished - Aug 10 1994

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Advanced Glycosylation End Products
Diabetes Complications
Oxidants
Erythrocytes
Endothelial Cells
Blood Vessels
Probucol
IgG Receptors
Thiobarbituric Acid Reactive Substances
Endothelium
Antibodies
Advanced Glycosylation End Product-Specific Receptor
Immunoblotting
Transcription Factors
Ligands
Morbidity
Mortality
Liver

All Science Journal Classification (ASJC) codes

  • General

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Advanced glycation end products (AGEs) on the surface of diabetic erythrocytes bind to the vessel wall via a specific receptor inducing oxidant stress in the vasculature : A link between surface-associated AGEs and diabetic complications. / Wautier, J. L.; Wautier, M. P.; Schmidt, A. M.; Anderson, G. M.; Hori, O.; Zoukourian, C.; Capron, L.; Chappey, O.; Yan, S. D.; Brett, J.; Guillausseau, P. J.; Stern, David.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 91, No. 16, 10.08.1994, p. 7742-7746.

Research output: Contribution to journalArticle

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abstract = "Vascular complications are an important cause of morbidity and mortality in patients with diabetes. The extent of vascular complications has been linked statistically to enhanced adherence of diabetic erythrocytes to endothelial cells (ECs) and to the accumulation of a class of glycated proteins termed advanced glycation end products (AGEs). We hypothesized that formation of AGEs on the surface of diabetic erythrocytes could mediate their interaction with ECs leading to binding and induction of vascular dysfunction. Enhanced binding of diabetic erythrocytes to ECs was blocked by preincubation of erythrocytes with anti-AGE IgG or preincubation of ECs with antibodies to the receptor for AGE (RAGE). Immunoblotting of cultured human ECs and immunostaining of normal/diabetic human tissue confirmed the presence of RAGE in the vessel wall. Binding of diabetic erythrocytes to endothelium generated an oxidant stress, as measured by production of thiobarbituric acid-reactive substances (TBARS) and activation of the transcription factor NF-κB, both of which were blocked by probucol or anti-RAGE IgG. Erythrocytes from diabetic rats infused into normal rats had an accelerated, early phase of clearance that was prevented, in part, by antibody to RAGE. Liver tissue from rats infused with diabetic erythrocytes showed elevated levels of TBARS, which was prevented by pretreatment with anti-RAGE IgG or probucol. Thus, erythrocyte surface AGEs can function as ligands that interact with RAGE on endothelium. The extensive contact of diabetic erythrocytes bearing surface- associated AGEs with vessel wall RAGE could be important in the development of vascular complications.",
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AU - Wautier, M. P.

AU - Schmidt, A. M.

AU - Anderson, G. M.

AU - Hori, O.

AU - Zoukourian, C.

AU - Capron, L.

AU - Chappey, O.

AU - Yan, S. D.

AU - Brett, J.

AU - Guillausseau, P. J.

AU - Stern, David

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