Skip to main content
PMC home page
The American Journal of Pathology logoLink to The American Journal of Pathology
. 1995 Mar;146(3):688–694.

Expression of Receptors for Advanced Glycation End Products in Peripheral Occlusive Vascular Disease

U Ritthaler, Y Deng, Y Zhang, J Greten, M Abel, B Sido, J Allenberg, G Otto, H Roth, A Bierhaus, R Ziegler, A-M Schmidt, R Waldherr, P Wahl, D M Stern, P P Nawroth
PMCID: PMC1869189  PMID: 7887450

Abstract

The cellular interactions of advanced glycation end products (AGEs), which have been hypothesized to contribute to the development of vascular lesions, occur, at least in part, through thei binding to a novel integral membrane protein, the receptor for AGEs (RAGE). Studies of human vascular segments show that endothelial RAGE expression at the antigen and mRNA level was variable and usually at low levels in samples from healthy individuals. In contrast, patients with arange of peripheral occlusive vascular diseases, with or without underlying diabetes, demonstrated prominent enhancement of endothelial RAGE expression. Smooth muscle cells and nerves in the vessel wall showed constitutively high levels of RAGE expression that were unchanged with aging (from 1 to 92 years) or by the presence of vascular disease, These data suggest that RAGE is likely to have ligands other than AGEs, and that multiple factors in addition to AGEs impact on its expression. Taken together, our findings suggest that RAGE may contribute to the pathogenesis of a range of vascular disorders.

Full text

PDF
688

Images in this article

690Figure 1
on p.690
692Figure 3
on p.692

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Brett J., Schmidt A. M., Yan S. D., Zou Y. S., Weidman E., Pinsky D., Nowygrod R., Neeper M., Przysiecki C., Shaw A. Survey of the distribution of a newly characterized receptor for advanced glycation end products in tissues. Am J Pathol. 1993 Dec;143(6):1699–1712. [PMC free article] [PubMed] [Google Scholar]
  2. Brownlee M., Cerami A., Vlassara H. Advanced glycosylation end products in tissue and the biochemical basis of diabetic complications. N Engl J Med. 1988 May 19;318(20):1315–1321. doi: 10.1056/NEJM198805193182007. [DOI] [PubMed] [Google Scholar]
  3. Dyer D. G., Blackledge J. A., Thorpe S. R., Baynes J. W. Formation of pentosidine during nonenzymatic browning of proteins by glucose. Identification of glucose and other carbohydrates as possible precursors of pentosidine in vivo. J Biol Chem. 1991 Jun 25;266(18):11654–11660. [PubMed] [Google Scholar]
  4. Esposito C., Gerlach H., Brett J., Stern D., Vlassara H. Endothelial receptor-mediated binding of glucose-modified albumin is associated with increased monolayer permeability and modulation of cell surface coagulant properties. J Exp Med. 1989 Oct 1;170(4):1387–1407. doi: 10.1084/jem.170.4.1387. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Fraser I., Hughes D., Gordon S. Divalent cation-independent macrophage adhesion inhibited by monoclonal antibody to murine scavenger receptor. Nature. 1993 Jul 22;364(6435):343–346. doi: 10.1038/364343a0. [DOI] [PubMed] [Google Scholar]
  6. Kirstein M., Aston C., Hintz R., Vlassara H. Receptor-specific induction of insulin-like growth factor I in human monocytes by advanced glycosylation end product-modified proteins. J Clin Invest. 1992 Aug;90(2):439–446. doi: 10.1172/JCI115879. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Kirstein M., Brett J., Radoff S., Ogawa S., Stern D., Vlassara H. Advanced protein glycosylation induces transendothelial human monocyte chemotaxis and secretion of platelet-derived growth factor: role in vascular disease of diabetes and aging. Proc Natl Acad Sci U S A. 1990 Nov;87(22):9010–9014. doi: 10.1073/pnas.87.22.9010. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Makita Z., Radoff S., Rayfield E. J., Yang Z., Skolnik E., Delaney V., Friedman E. A., Cerami A., Vlassara H. Advanced glycosylation end products in patients with diabetic nephropathy. N Engl J Med. 1991 Sep 19;325(12):836–842. doi: 10.1056/NEJM199109193251202. [DOI] [PubMed] [Google Scholar]
  9. Miyata T., Oda O., Inagi R., Iida Y., Araki N., Yamada N., Horiuchi S., Taniguchi N., Maeda K., Kinoshita T. beta 2-Microglobulin modified with advanced glycation end products is a major component of hemodialysis-associated amyloidosis. J Clin Invest. 1993 Sep;92(3):1243–1252. doi: 10.1172/JCI116696. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Monnier V. M., Vishwanath V., Frank K. E., Elmets C. A., Dauchot P., Kohn R. R. Relation between complications of type I diabetes mellitus and collagen-linked fluorescence. N Engl J Med. 1986 Feb 13;314(7):403–408. doi: 10.1056/NEJM198602133140702. [DOI] [PubMed] [Google Scholar]
  11. Neeper M., Schmidt A. M., Brett J., Yan S. D., Wang F., Pan Y. C., Elliston K., Stern D., Shaw A. Cloning and expression of a cell surface receptor for advanced glycosylation end products of proteins. J Biol Chem. 1992 Jul 25;267(21):14998–15004. [PubMed] [Google Scholar]
  12. Pamplona R., Bellmunt M. J., Portero M., Prat J. Mechanisms of glycation in atherogenesis. Med Hypotheses. 1993 Mar;40(3):174–181. doi: 10.1016/0306-9877(93)90207-7. [DOI] [PubMed] [Google Scholar]
  13. Schmidt A. M., Hasu M., Popov D., Zhang J. H., Chen J., Yan S. D., Brett J., Cao R., Kuwabara K., Costache G. Receptor for advanced glycation end products (AGEs) has a central role in vessel wall interactions and gene activation in response to circulating AGE proteins. Proc Natl Acad Sci U S A. 1994 Sep 13;91(19):8807–8811. doi: 10.1073/pnas.91.19.8807. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Schmidt A. M., Vianna M., Gerlach M., Brett J., Ryan J., Kao J., Esposito C., Hegarty H., Hurley W., Clauss M. Isolation and characterization of two binding proteins for advanced glycosylation end products from bovine lung which are present on the endothelial cell surface. J Biol Chem. 1992 Jul 25;267(21):14987–14997. [PubMed] [Google Scholar]
  15. Schmidt A. M., Yan S. D., Brett J., Mora R., Nowygrod R., Stern D. Regulation of human mononuclear phagocyte migration by cell surface-binding proteins for advanced glycation end products. J Clin Invest. 1993 May;91(5):2155–2168. doi: 10.1172/JCI116442. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Schnider S. L., Kohn R. R. Glucosylation of human collagen in aging and diabetes mellitus. J Clin Invest. 1980 Nov;66(5):1179–1181. doi: 10.1172/JCI109950. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Sell D. R., Monnier V. M. Structure elucidation of a senescence cross-link from human extracellular matrix. Implication of pentoses in the aging process. J Biol Chem. 1989 Dec 25;264(36):21597–21602. [PubMed] [Google Scholar]
  18. Tezuka M., Koyama N., Morisaki N., Saito Y., Yoshida S., Araki N., Horiuchi S. Angiogenic effects of advanced glycation end products of the Maillard reaction on cultured human umbilical cord vein endothelial cells. Biochem Biophys Res Commun. 1993 Jun 15;193(2):674–680. doi: 10.1006/bbrc.1993.1677. [DOI] [PubMed] [Google Scholar]
  19. Vitek M. P., Bhattacharya K., Glendening J. M., Stopa E., Vlassara H., Bucala R., Manogue K., Cerami A. Advanced glycation end products contribute to amyloidosis in Alzheimer disease. Proc Natl Acad Sci U S A. 1994 May 24;91(11):4766–4770. doi: 10.1073/pnas.91.11.4766. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Vlassara H., Brownlee M., Manogue K. R., Dinarello C. A., Pasagian A. Cachectin/TNF and IL-1 induced by glucose-modified proteins: role in normal tissue remodeling. Science. 1988 Jun 10;240(4858):1546–1548. doi: 10.1126/science.3259727. [DOI] [PubMed] [Google Scholar]
  21. Vlassara H., Fuh H., Makita Z., Krungkrai S., Cerami A., Bucala R. Exogenous advanced glycosylation end products induce complex vascular dysfunction in normal animals: a model for diabetic and aging complications. Proc Natl Acad Sci U S A. 1992 Dec 15;89(24):12043–12047. doi: 10.1073/pnas.89.24.12043. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Vlassara H., Moldawer L., Chan B. Macrophage/monocyte receptor for nonenzymatically glycosylated protein is upregulated by cachectin/tumor necrosis factor. J Clin Invest. 1989 Dec;84(6):1813–1820. doi: 10.1172/JCI114366. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. 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. 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. Proc Natl Acad Sci U S A. 1994 Aug 2;91(16):7742–7746. doi: 10.1073/pnas.91.16.7742. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Yan S. D., Chen X., Schmidt A. M., Brett J., Godman G., Zou Y. S., Scott C. W., Caputo C., Frappier T., Smith M. A. Glycated tau protein in Alzheimer disease: a mechanism for induction of oxidant stress. Proc Natl Acad Sci U S A. 1994 Aug 2;91(16):7787–7791. doi: 10.1073/pnas.91.16.7787. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Yan S. D., Schmidt A. M., Anderson G. M., Zhang J., Brett J., Zou Y. S., Pinsky D., Stern D. Enhanced cellular oxidant stress by the interaction of advanced glycation end products with their receptors/binding proteins. J Biol Chem. 1994 Apr 1;269(13):9889–9897. [PubMed] [Google Scholar]
  26. Yang Z., Makita Z., Horii Y., Brunelle S., Cerami A., Sehajpal P., Suthanthiran M., Vlassara H. Two novel rat liver membrane proteins that bind advanced glycosylation endproducts: relationship to macrophage receptor for glucose-modified proteins. J Exp Med. 1991 Sep 1;174(3):515–524. doi: 10.1084/jem.174.3.515. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Zhang Y. M., Bachmann S., Hemmer C., van Lunzen J., von Stemm A., Kern P., Dietrich M., Ziegler R., Waldherr R., Nawroth P. P. Vascular origin of Kaposi's sarcoma. Expression of leukocyte adhesion molecule-1, thrombomodulin, and tissue factor. Am J Pathol. 1994 Jan;144(1):51–59. [PMC free article] [PubMed] [Google Scholar]

Articles from The American Journal of Pathology are provided here courtesy of American Society for Investigative Pathology

RESOURCES