Receptor for advanced glycation end products (AGEs) has a central role in vessel wall interactions and gene activation in response to circulating AGE proteins

Ann Marie Schmidt, Mirela Hasu, Doina Popov, Jing Hua Zhang, Jingxian Chen, Shi Du Yan, Jerold Brett, Rong Cao, Keisuke Kuwabara, Gabriela Costache, Nicolae Simionescu, Maya Simionescu, David Stern

Research output: Contribution to journalArticle

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Abstract

The extended interaction of aldoses with proteins or lipids results in nonenzymatic glycation and oxidation, ultimately forming AGEs, the presence of which in the plasma and vessel wall is associated with diabetic vascular complications. We show here that AGE albumin in the intravascular space interacts with the vessel wall via binding to an integral membrane protein, receptor for AGE (RAGE), a member of the immunoglobulin superfamily, resulting in clearance from the plasma and induction of interleukin 6 mRNA. Intravenously infused 125 I-AGE albumin showed a rapid phase of plasma clearance with deposition in several organs. Rapid removal of 125 I-AGE albumin from the plasma was prevented by administration of a soluble, truncated form of RAGE, which blocked binding of 125 I-labeled AGE albumin to cultured endothelial cells and mononuclear phagocytes, as well as by pretreatment with anti-RAGE IgG. Ultrastructural studies with AGE albumin- colloidal gold conjugates perfused in situ showed that in murine coronary vasculature this probe was taken up by endothelial plasmalemmal vesicles followed by transport either to the abluminal surface or by accumulation in intracellular vesicular structures reminiscent of endosomes and lysosomes. Consequences of AGE-RAGE interaction included induction of interleukin 6 mRNA expression in mice. These data indicate that RAGE mediates the interaction of AGEs with the vessel wall, both for removal of these glycated proteins from the plasma and for changes in gene expression.

Original languageEnglish (US)
Pages (from-to)8807-8811
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume91
Issue number19
DOIs
StatePublished - Sep 13 1994

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Transcriptional Activation
Albumins
Proteins
Interleukin-6
IgG Receptors
Diabetic Angiopathies
Gold Colloid
Transport Vesicles
Messenger RNA
Endosomes
Phagocytes
Lysosomes
Serum Albumin
Immunoglobulins
Blood Proteins
Cultured Cells
Membrane Proteins
Endothelial Cells
Advanced Glycosylation End Product-Specific Receptor
Lipids

All Science Journal Classification (ASJC) codes

  • General

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Receptor for advanced glycation end products (AGEs) has a central role in vessel wall interactions and gene activation in response to circulating AGE proteins. / Schmidt, Ann Marie; Hasu, Mirela; Popov, Doina; Zhang, Jing Hua; Chen, Jingxian; Yan, Shi Du; Brett, Jerold; Cao, Rong; Kuwabara, Keisuke; Costache, Gabriela; Simionescu, Nicolae; Simionescu, Maya; Stern, David.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 91, No. 19, 13.09.1994, p. 8807-8811.

Research output: Contribution to journalArticle

Schmidt, Ann Marie ; Hasu, Mirela ; Popov, Doina ; Zhang, Jing Hua ; Chen, Jingxian ; Yan, Shi Du ; Brett, Jerold ; Cao, Rong ; Kuwabara, Keisuke ; Costache, Gabriela ; Simionescu, Nicolae ; Simionescu, Maya ; Stern, David. / Receptor for advanced glycation end products (AGEs) has a central role in vessel wall interactions and gene activation in response to circulating AGE proteins. In: Proceedings of the National Academy of Sciences of the United States of America. 1994 ; Vol. 91, No. 19. pp. 8807-8811.
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