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. 1993 Dec;143(6):1649–1656.

Immunohistochemical localization of advanced glycosylation end products in coronary atheroma and cardiac tissue in diabetes mellitus.

Y Nakamura 1, Y Horii 1, T Nishino 1, H Shiiki 1, Y Sakaguchi 1, T Kagoshima 1, K Dohi 1, Z Makita 1, H Vlassara 1, R Bucala 1
PMCID: PMC1887270  PMID: 8256853

Abstract

Advanced glycosylation end products (AGEs) accumulate on long-lived extracellular matrix proteins and have been implicated in the micro- and macrovascular complications of diabetes mellitus. Within the arterial wall, AGE-modified proteins increase vascular permeability, inactivate nitric oxide activity, and induce the release of growth-promoting cytokines. Recently developed anti-AGE antibodies were used in an immunohistochemical analysis of coronary arteries obtained from type II diabetic and nondiabetic patients. High levels of AGE reactivity were observed within the atherosclerotic plaque present in vessels from selected patients with diabetes. Considered together with the pathological effects of AGEs on vascular wall homeostasis, these data support the role of advanced glycosylation in the rapidly progressive atherosclerosis associated with diabetes mellitus.

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Selected References

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

  1. Ahmed M. U., Thorpe S. R., Baynes J. W. Identification of N epsilon-carboxymethyllysine as a degradation product of fructoselysine in glycated protein. J Biol Chem. 1986 Apr 15;261(11):4889–4894. [PubMed] [Google Scholar]
  2. BRYFOGLE J. W., BRADLEY R. F. The vascular complications of diabetes mellitus; a clinical study. Diabetes. 1957 Mar-Apr;6(2):159–167. doi: 10.2337/diab.6.2.159. [DOI] [PubMed] [Google Scholar]
  3. Bern M. M. Platelet functions in diabetes mellitus. Diabetes. 1978 Mar;27(3):342–350. doi: 10.2337/diab.27.3.342. [DOI] [PubMed] [Google Scholar]
  4. 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]
  5. Brownlee M., Vlassara H., Cerami A. Nonenzymatic glycosylation products on collagen covalently trap low-density lipoprotein. Diabetes. 1985 Sep;34(9):938–941. doi: 10.2337/diab.34.9.938. [DOI] [PubMed] [Google Scholar]
  6. Brownlee M., Vlassara H., Kooney A., Ulrich P., Cerami A. Aminoguanidine prevents diabetes-induced arterial wall protein cross-linking. Science. 1986 Jun 27;232(4758):1629–1632. doi: 10.1126/science.3487117. [DOI] [PubMed] [Google Scholar]
  7. Bucala R., Cerami A. Advanced glycosylation: chemistry, biology, and implications for diabetes and aging. Adv Pharmacol. 1992;23:1–34. doi: 10.1016/s1054-3589(08)60961-8. [DOI] [PubMed] [Google Scholar]
  8. Bucala R., Tracey K. J., Cerami A. Advanced glycosylation products quench nitric oxide and mediate defective endothelium-dependent vasodilatation in experimental diabetes. J Clin Invest. 1991 Feb;87(2):432–438. doi: 10.1172/JCI115014. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Chang J. C., Ulrich P. C., Bucala R., Cerami A. Detection of an advanced glycosylation product bound to protein in situ. J Biol Chem. 1985 Jul 5;260(13):7970–7974. [PubMed] [Google Scholar]
  10. Dybdahl H., Ledet T. Diabetic macroangiopathy. Quantitative histopathological studies of the extramural coronary arteries from type 2 (non-insulin-dependent) diabetic patients. Diabetologia. 1987 Nov;30(11):882–886. [PubMed] [Google Scholar]
  11. 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]
  12. FOWLER N. O., GUERON M., ROWLANDS D. T., Jr Primary myocardial disease. Circulation. 1961 Apr;23:498–508. doi: 10.1161/01.cir.23.4.498. [DOI] [PubMed] [Google Scholar]
  13. Hammes H. P., Martin S., Federlin K., Geisen K., Brownlee M. Aminoguanidine treatment inhibits the development of experimental diabetic retinopathy. Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11555–11558. doi: 10.1073/pnas.88.24.11555. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hogan M., Cerami A., Bucala R. Advanced glycosylation endproducts block the antiproliferative effect of nitric oxide. Role in the vascular and renal complications of diabetes mellitus. J Clin Invest. 1992 Sep;90(3):1110–1115. doi: 10.1172/JCI115928. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Horiuchi S., Araki N., Morino Y. Immunochemical approach to characterize advanced glycation end products of the Maillard reaction. Evidence for the presence of a common structure. J Biol Chem. 1991 Apr 25;266(12):7329–7332. [PubMed] [Google Scholar]
  16. Kihara M., Schmelzer J. D., Poduslo J. F., Curran G. L., Nickander K. K., Low P. A. Aminoguanidine effects on nerve blood flow, vascular permeability, electrophysiology, and oxygen free radicals. Proc Natl Acad Sci U S A. 1991 Jul 15;88(14):6107–6111. doi: 10.1073/pnas.88.14.6107. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. 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]
  18. Makita Z., Vlassara H., Cerami A., Bucala R. Immunochemical detection of advanced glycosylation end products in vivo. J Biol Chem. 1992 Mar 15;267(8):5133–5138. [PubMed] [Google Scholar]
  19. Makita Z., Vlassara H., Rayfield E., Cartwright K., Friedman E., Rodby R., Cerami A., Bucala R. Hemoglobin-AGE: a circulating marker of advanced glycosylation. Science. 1992 Oct 23;258(5082):651–653. doi: 10.1126/science.1411574. [DOI] [PubMed] [Google Scholar]
  20. Monnier V. M., Kohn R. R., Cerami A. Accelerated age-related browning of human collagen in diabetes mellitus. Proc Natl Acad Sci U S A. 1984 Jan;81(2):583–587. doi: 10.1073/pnas.81.2.583. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Nakayama H., Taneda S., Kuwajima S., Aoki S., Kuroda Y., Misawa K., Nakagawa S. Production and characterization of antibodies to advanced glycation products on proteins. Biochem Biophys Res Commun. 1989 Jul 31;162(2):740–745. doi: 10.1016/0006-291x(89)92372-3. [DOI] [PubMed] [Google Scholar]
  22. Njoroge F. G., Monnier V. M. The chemistry of the Maillard reaction under physiological conditions: a review. Prog Clin Biol Res. 1989;304:85–107. [PubMed] [Google Scholar]
  23. Njoroge F. G., Sayre L. M., Monnier V. M. Detection of D-glucose-derived pyrrole compounds during Maillard reaction under physiological conditions. Carbohydr Res. 1987 Sep 15;167:211–220. doi: 10.1016/0008-6215(87)80280-x. [DOI] [PubMed] [Google Scholar]
  24. Pongor S., Ulrich P. C., Bencsath F. A., Cerami A. Aging of proteins: isolation and identification of a fluorescent chromophore from the reaction of polypeptides with glucose. Proc Natl Acad Sci U S A. 1984 May;81(9):2684–2688. doi: 10.1073/pnas.81.9.2684. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Rosai J., Lascano E. F. Basophilic (mucoid) degeneration of myocardium: a disorder of glycogen metabolism. Am J Pathol. 1970 Oct;61(1):99–116. [PMC free article] [PubMed] [Google Scholar]
  26. Ross R. The pathogenesis of atherosclerosis--an update. N Engl J Med. 1986 Feb 20;314(8):488–500. doi: 10.1056/NEJM198602203140806. [DOI] [PubMed] [Google Scholar]
  27. Saenz de Tejada I., Goldstein I., Azadzoi K., Krane R. J., Cohen R. A. Impaired neurogenic and endothelium-mediated relaxation of penile smooth muscle from diabetic men with impotence. N Engl J Med. 1989 Apr 20;320(16):1025–1030. doi: 10.1056/NEJM198904203201601. [DOI] [PubMed] [Google Scholar]
  28. Sell D. R., Lapolla A., Odetti P., Fogarty J., Monnier V. M. Pentosidine formation in skin correlates with severity of complications in individuals with long-standing IDDM. Diabetes. 1992 Oct;41(10):1286–1292. doi: 10.2337/diab.41.10.1286. [DOI] [PubMed] [Google Scholar]
  29. Smith P. R., Somani H. H., Thornalley P. J., Benn J., Sonksen P. H. Evidence against the formation of 2-amino-6-(2-formyl-5-hydroxymethyl-pyrrol-1-yl)-hexanoic acid ('pyrraline') as an early-stage product or advanced glycation end product in non-enzymic protein glycation. Clin Sci (Lond) 1993 Jan;84(1):87–93. doi: 10.1042/cs0840087. [DOI] [PubMed] [Google Scholar]
  30. Soulis-Liparota T., Cooper M., Papazoglou D., Clarke B., Jerums G. Retardation by aminoguanidine of development of albuminuria, mesangial expansion, and tissue fluorescence in streptozocin-induced diabetic rat. Diabetes. 1991 Oct;40(10):1328–1334. doi: 10.2337/diab.40.10.1328. [DOI] [PubMed] [Google Scholar]
  31. Steinberg D., Parthasarathy S., Carew T. E., Khoo J. C., Witztum J. L. Beyond cholesterol. Modifications of low-density lipoprotein that increase its atherogenicity. N Engl J Med. 1989 Apr 6;320(14):915–924. doi: 10.1056/NEJM198904063201407. [DOI] [PubMed] [Google Scholar]
  32. Vlassara H., Brownlee M., Cerami A. High-affinity-receptor-mediated uptake and degradation of glucose-modified proteins: a potential mechanism for the removal of senescent macromolecules. Proc Natl Acad Sci U S A. 1985 Sep;82(17):5588–5592. doi: 10.1073/pnas.82.17.5588. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. 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]

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