Hostname: page-component-8448b6f56d-m8qmq Total loading time: 0 Render date: 2024-04-16T07:34:45.345Z Has data issue: false hasContentIssue false
  • English
  • Français

The receptor for advanced glycation endproducts (RAGE) and cardiovascular disease

Published online by Cambridge University Press:  12 March 2009

Shi Fang Yan ,
Ravichandran Ramasamy  and
Ann Marie Schmidt
Shi Fang Yan
Affiliation:
Division of Surgical Science, Department of Surgery, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
Ravichandran Ramasamy
Affiliation:
Division of Surgical Science, Department of Surgery, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
Ann Marie Schmidt*
Affiliation:
Division of Surgical Science, Department of Surgery, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
*
*Corresponding author: Ann Marie Schmidt, Division of Surgical Science, Department of Surgery, Columbia University, 630 West 168th Street, P&S 17-501, New York, NY 10032, USA. Tel: +1 212 305 6406; Fax: +1 212 3055337; E-mail: ams11@columbia.edu
Get access Rights & Permissions [Opens in a new window]

Abstract

Recent and compelling investigation has expanded our view of the biological settings in which the products of nonenzymatic glycation and oxidation of proteins and lipids – the advanced glycation endproducts (AGEs) – form and accumulate. Beyond diabetes, natural ageing and renal failure, AGEs form in inflammation, oxidative stress and in ischaemia–reperfusion. The chief signal transduction receptor for AGEs – the receptor for AGEs (RAGE) – is a multiligand-binding member of the immunoglobulin superfamily. In addition to AGEs, RAGE binds certain members of the S100/calgranulin family, high-mobility group box 1 (HMGB1), and β-amyloid peptide and β-sheet fibrils. Recent studies demonstrate beneficial effects of RAGE antagonism and genetic deletion in rodent models of atherosclerosis and ischaemia–reperfusion injury in the heart and great vessels. Experimental evidence is accruing that RAGE ligand generation and release during ischaemia–reperfusion may signal through RAGE, thus suggesting that antagonism of this receptor might provide a novel form of therapeutic intervention in heart disease. However, it is plausible that innate, tissue-regenerative roles for these RAGE ligands may also impact the failing heart – perhaps through RAGE and/or distinct receptors. In this review, we focus on RAGE and the consequences of its activation in the cardiovasculature.

Type
Review Article
Information
Expert Reviews in Molecular Medicine , Volume 11 , July 2009 , e9
Copyright
Copyright © Cambridge University Press 2009

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

References

1Stevens, V.J. et al. (1977) Nonenzymatic glycosylation of hemoglobin. Journal of Biological Chemistry 252, 2998-3002CrossRefGoogle ScholarPubMed
2Day, J. et al. (1979) Nonenzymatic glycosylation of rat albumin. Journal of Biological Chemistry 254, 9394-9400Google Scholar
3Schnider, S.L. and Kohn, R.R. (1980) Glucosylation of human collagen in aging and diabetes mellitus. Journal of Clinical Investigation 66, 1179-1181CrossRefGoogle ScholarPubMed
4Sensi, M.S. et al. (1991) Advanced nonenzymatic glycation endproducts (AGEs): their relevance to aging and the pathogenesis of late diabetic complications. Diabetes Research 16, 1-9Google Scholar
5Brownlee, M. (1992) Glycation products and the pathogenesis of diabetic complications. Diabetes Care 15, 1835-1843Google Scholar
6Miyata, T. et al. (1996) Pathophysiology of advanced glycation endproducts in renal failure. Nephrology Dialysis Transplantation 11, 27-30Google Scholar
7Dawnay, A. and Millar, D.J. (1998) The pathogenesis and consequences of AGE formation in uraemia and its treatment. Cellular and Molecular Biology (Noisy-le-grand) 44, 1081-1094Google Scholar
8Sakata, N. et al. (1995) Nonenzymatic glycation and extractability of collagen in human atherosclerotic plaques. Atherosclerosis 116, 63-75Google Scholar
9Mulder, D.J. et al. (2006) Skin autofluorescence, a novel marker for glycemic and oxidative stress-derived advanced glycation endproducts: an overview of current clinical studies, evidence and limitations. Diabetes Technology and Therapeutics 8, 523-535CrossRefGoogle ScholarPubMed
10Münch, G. et al. (1997) Determination of advanced glycation end products in serum by fluorescence spectroscopy and competitive ELISA. European Journal of Clinical Chemistry and Clinical Biochemistry 35, 669-677Google ScholarPubMed
11Matsumoto, T. et al. (2007) Measurement of advanced glycation endproducts in skin of patients with rheumatoid arthritis, osteoarthritis, and dialysis-related spondyloarthropathy using non-invasive methods. Rheumatology International 28, 157-160CrossRefGoogle ScholarPubMed
12De Leeuw, K. et al. (2007) Accumulation of advanced glycation end products in patients with systemic lupus erythematous. Rheumatology (Oxford) 46, 1551-1556Google Scholar
13Charney, D.I. et al. (1993) Atherosclerosis in chronic renal failure. Current Opinion in Nephrology and Hypertension 2, 876-882CrossRefGoogle ScholarPubMed
14Farhey, Y. and Hess, E.V. (1997) Accelerated atherosclerosis and coronary diseases in SLE. Lupus 6, 572-577Google Scholar
15Bucciarelli, L.G. et al. (2006) Receptor for advanced glycation endproducts: key modulator of myocardial ischemic injury. Circulation 113, 1226-1234Google Scholar
16Takizawa, S. et al. (2007) A novel inhibitor of advanced glycation end endoplasmic reticulum stress reduces infarct volume in rat focal cerebral ischemia. Brain Research 1183, 124-137CrossRefGoogle ScholarPubMed
17Aleshin, A. et al. (2008) RAGE modulates myocardial injury consequent to LAD infarction via impact on JNK and STAT signaling in a murine model. American Journal of Physiology – Heart and Circulatory Physiology 294, H1823-H1832Google Scholar
18Bucciarelli, L.G. et al. (2008) RAGE and modulation of ischemic injury in the diabetic myocardium. Diabetes 57, 1941-1951CrossRefGoogle ScholarPubMed
19Schmidt, A.M. et al. (1992) Isolation and characterization of binding proteins for advanced glycosylation endproducts from lung tissue which are present on the endothelial cell surface. Journal of Biological Chemistry 267, 14987-14997CrossRefGoogle Scholar
20Neeper, M. et al. (1992) Cloning and expression of RAGE: a cell surface receptor for advanced glycosylation end products of proteins. Journal of Biological Chemistry 267, 14998-15004CrossRefGoogle Scholar
21Horiuchi, S., Sakamoto, Y. and Sakai, M. (2003) Scavenger receptors for oxidized and glycated proteins. Amino Acids 25, 283-292CrossRefGoogle ScholarPubMed
22Ohgami, N. et al. (2002) CD36 serves a receptor for advanced glycation endproducts (AGEs). Journal of Diabetes and its Complications 16, 56-59Google Scholar
23Li, Y.M. et al. (1996) Molecular identity and cellular distribution of advanced glycation endproduct receptors: relationship of p60 to OST-48 and p90 to 80 K-H membrane proteins. Proceedings of the National Academy of Sciences of the United States of America 93, 11047-11052Google Scholar
24Lu, C. et al. (2004) Advanced glycation endproduct (AGE) receptor 1 is a negative regulator of the inflammatory response to AGE in mesangial cells. Proceedings of the National Academy of Sciences of the United States of America 101, 11767-11772Google Scholar
25McFarlane, S. et al. (2005) Characterization of the advanced glycation endproduct receptor complex in the retinal pigment epithelium. British Journal of Ophthalmology 89, 107-112CrossRefGoogle ScholarPubMed
26Taguchi, A. et al. (2000) Blockade of amphoterin/RAGE signalling suppresses tumor growth and metastases. Nature 405, 354-360CrossRefGoogle Scholar
27Lander, H.M. et al. (1997) Activation of the receptor for advanced glycation endproducts triggers a p21(ras)-dependent mitogen-activated protein kinase pathway regulated by oxidant stress. Journal of Biological Chemistry 272, 17810-17814Google Scholar
28Marsche, G. et al. (2007) Hypochlorite-modified albumin colocalizes with RAGE in the artery wall and promotes MCP-1 expression via the RAGE-ERK 1/2 MAP-kinase pathway. The FASEB Journal 21, 1145-1152CrossRefGoogle Scholar
29Zeng, S. et al. (2004) Blockade of receptor for advanced glycation endproducts (RAGE) attenuates ischemia and reperfusion injury in the liver in mice. Hepatology 39, 422-432Google Scholar
30Reddy, M.A. et al. (2006) Key role of Src kinase in S100b-induced activation of the receptor for advanced glycation endproducts in vascular smooth muscle cells. Journal of Biological Chemistry 281, 13685-13693Google Scholar
31Sakaguchi, T. et al. (2003) Arterial restenosis: central role of RAGE-dependent neointimal expansion. Journal of Clinical Investigation 111, 959-972Google Scholar
32Bianchi, R. et al. (2007) S100b binding to RAGE in microglia stimulates cox-2 expression. Journal of Leukocyte Biology 81, 108-118CrossRefGoogle ScholarPubMed
33Fukami, K. et al. (2004) AGEs activate mesangial TGF-beta-Smad signaling via an angiotensin II type 1 receptor interaction. Kidney International 66, 2137-2147Google Scholar
34Vincent, A.M. et al. (2007) Receptor for advanced glycation end products activation injures primary sensory neurons via oxidative stress. Endocrinology 148, 548-558CrossRefGoogle ScholarPubMed
35Yan, S.D. et al. (1994) Enhanced cellular oxidant stress by the interaction of advanced glycation end products with their receptors/binding proteins. Journal of Biological Chemistry 269, 9889-9897Google Scholar
36Huttunen, H.J., Kuja-Panula, J. and Rauvala, H. (2002) Receptor for advanced glycation end products (RAGE) signaling induces CREB-dependent chromogranin expression during neuronal differentiation. Journal of Biological Chemistry 277, 38635-38646CrossRefGoogle ScholarPubMed
37Chang, J.S. et al. (2008) Oxygen deprivation triggers upregulation of early growth response-1 by the receptor for advanced glycation end products. Circulation Research 102, 905-913CrossRefGoogle ScholarPubMed
38Hofmann, M.A. et al. (1999) RAGE mediates a novel proinflammatory axis: a central cell surface receptor for S100/calgranulin polypeptides. Cell 97, 889-901CrossRefGoogle Scholar
39Yan, S.D. et al. (1996) RAGE and amyloid-beta peptide neurotoxicity in Alzheimer's disease. Nature 382, 685-691CrossRefGoogle ScholarPubMed
40Arancio, O. et al. (2004) RAGE potentiates Abeta-induced perturbation of neuronal function in transgenic mice. EMBO Journal 23, 4096-4105CrossRefGoogle ScholarPubMed
41Chavakis, T. et al. (2003) The Pattern Recognition Receptor (RAGE) is a counterreceptor for leukocyte integrins: a novel pathway for inflammatory cell recruitment. Journal of Experimental Medicine 198, 1507-1515CrossRefGoogle ScholarPubMed
42Brett, J. et al. (1993) Tissue distribution of the receptor for advanced glycation endproducts (RAGE): expression in smooth muscle, cardiac myocytes, and neural tissue in addition to the vasculature. American Journal of Pathology 143, 1699-1712Google Scholar
43Tanji, N. et al. (2000) The expression of Advanced Glycation Endproducts and their cellular receptor RAGE in diabetic nephropathy and non-diabetic renal disease. Journal of the American Society of Nephrology 11, 1656-1666CrossRefGoogle Scholar
44Oimomi, M. et al. (1989) Age- and diabetes-accelerated glycation in the human aorta. Archives of Gerontology and Geriatrics 8, 123-127CrossRefGoogle ScholarPubMed
45Burke, A.P. et al. (2004) Morphologic findings of coronary atherosclerotic plaques in diabetics: a postmorten study. Arteriosclerosis, Thrombosis, and Vascular Biology 24, 1266-1271CrossRefGoogle Scholar
46Inoue, K. et al. (2007) HMGB1 expression by activated vascular smooth muscle cells in advanced human atherosclerosis plaques. Cardiovascular Pathology 16, 136-143CrossRefGoogle ScholarPubMed
47Kalinina, N. et al. (2004) Increased expression of the DNA binding cytokine HMGB1 in human atherosclerotic lesions: role of activated macrophages and cytokines. Arteriosclerosis, Thrombosis, and Vascular Biology 24, 2320-2325CrossRefGoogle ScholarPubMed
48Park, L. et al. (1998) Suppression of accelerated diabetic atherosclerosis by soluble receptor for AGE (sRAGE). Nature Med 4, 1025-1031CrossRefGoogle Scholar
49Kislinger, T. et al. (2001) RAGE mediates inflammation and enhanced expression of tissue factor in the vasculature of diabetic apolipoprotein E null mice. Arteriosclerosis, Thrombosis, and Vascular Biology 21, 905-910Google Scholar
50Bucciarelli, L.G. et al. (2002) RAGE blockade stabilizes established atherosclerosis in diabetic apolipoprotein E null mice. Circulation 106, 2827-2835Google Scholar
51Wendt, T. et al. (2006) RAGE modulates vascular inflammation and atherosclerosis in a murine model of type 2 diabetes. Atherosclerosis 185, 70-77CrossRefGoogle Scholar
52Soro-Paavonen, A. et al. (2008) Receptor for advanced glycation endproducts (RAGE) deficiency attenuates the development of atherosclerosis in diabetes. Diabetes 57, 2461-2469Google Scholar
53Harja, E. et al. (2008) Vascular and inflammatory stresses mediate atherosclerosis via RAGE in apo E deficient mice. Journal of Clinical Investigation 118, 183-194CrossRefGoogle Scholar
54Roy, H. et al. (2006) VEGF-A, VEGF-D, VEGF-receptor-1, VEGF-receptor-2, NF-kB and RAGE in atherosclerotic lesions of diabetic Watanabe heritable hyperlipidemic rabbits. The FASEB Journal 20, 2159-2161Google Scholar
55Schmidt, A.M. et al. (1993) Regulation of human mononuclear phagocyte migration by cell surface-binding proteins for advanced glycation end products. Journal of Clinical Investigation 91, 2155-2168Google Scholar
56Kislinger, T. et al. (1999) N-ɛ (carboxymethyl)lysine modifications of proteins are ligands for RAGE that activate cell signalling pathways and modulate gene expression. Journal of Biological Chemistry 274, 31740-31749Google Scholar
57Rouhiainen, A. et al. (2004) Regulation of monocyte migration by amphoterin. Blood 104, 1174-1182Google Scholar
58Isoda, K. et al. (2008) Glycated LDL increased monocyte CC chemokine receptor 2 expression and monocyte chemoattractant protein-1 mediated chemotaxis. Atherosclerosis 198, 307-312Google Scholar
59Isoda, K. et al. (2007) AGE-BSA decreases ABCG1 expression and reduces macrophage cholesterol efflux to HDL. Atherosclerosis 192, 298-304CrossRefGoogle Scholar
60Ichikawa, K. et al. (1998) Advanced glycosylation endproducts induced tissue factor expression in human monocyte-like U937 cells and increased tissue factor expression in monocytes from diabetic patients. Atherosclerosis 136, 281-287CrossRefGoogle Scholar
61Ding, Y. et al. (2007) Phosphorylation of pleckstrin increases proinflammatory cytokine secretion by mononuclear phagocytes in diabetes mellitus. Journal of Immunology 179, 647-654CrossRefGoogle ScholarPubMed
62Shaw, S.S. et al. (2003) S100b-RAGE mediated augmentation of angiotensin II-induced activation of JAK2 in vascular smooth muscle cells is dependent on PLD2. Diabetes 52, 2381-2388Google Scholar
63Yoon, Y.W. et al. (2008) Pathobiological role of advanced glycation endproducts via mitogen-activated protein kinase dependent pathway in the diabetic vasculopathy. Experimental and Molecular Medicine 31, 398-406CrossRefGoogle Scholar
64Wu, S. et al. (2008) Involvement of Na+/H+ exchanger in advanced end products-induced proliferation of vascular smooth muscle cell. Biochemical and Biophysical Research Communications 375, 384-389CrossRefGoogle ScholarPubMed
65De Oliveira, S.C. et al. (2008) Modulation of CD36 protein expression by AGEs and insulin in aortic VSMCs from diabetic and non-diabetic rats. Nutrition, Metabolism and Cardiovascular Diseases 18, 23-30Google Scholar
66Zhou, Z. et al. (2003) Receptor for AGE (RAGE) mediates neointimal formation in response to arterial injury. Circulation 107, 2238-2243Google Scholar
67Hartog, J.W.L. et al. (2007) Advanced glycation end products and heart failure: pathophysiology of clinical implications. European Journal of Heart Failure 9, 1146-1155CrossRefGoogle ScholarPubMed
68Koyama, Y. et al. (2007) High serum level of pentosidine, an advanced glycation endproduct (AGE), is a risk factor of patients with heart failure. Journal of Cardiac Failure 13, 199-206CrossRefGoogle ScholarPubMed
69Hartog, J.W. et al. (2007) clinical and prognostic value of advanced glycation end products in chronic heart failure. European Heart Journal 28, 2879-2885CrossRefGoogle ScholarPubMed
70Van Heerebeek, L. et al. (2008) Diastolic stiffness of the failing diabetic heart: importance of fibrosis, advanced glycation end products, and myocyte resting tension. Circulation 117, 43-51CrossRefGoogle ScholarPubMed
71Koyama, Y. et al. (2008) Soluble receptor for advanced glycation endproducts (RAGE) is a prognostic factor for heart failure. Journal of Cardiac Failure 14, 133-198CrossRefGoogle ScholarPubMed
72Andrassy, M. et al. (2008) High mobility group box 1 in ischemia-reperfusion injury of the heart. Circulation 117, 3216-3226CrossRefGoogle ScholarPubMed
73Park, J.S. et al. (2004) Involvement of toll-like receptors 2 and 4 in cellular activation by high mobility group box 1 protein. Journal of Biological Chemistry 279, 7370-7377CrossRefGoogle ScholarPubMed
74Tsoporis, J.N. et al. (2005) S100b expression modulates left ventricular remodeling after myocardial infarction in mice. Circulation 111, 598-606Google Scholar
75Norton, G.R., Candy, G. and Woodiwiss, A.J. (1996) Aminoguanidine prevents the decreased myocardial compliance produced by streptozotocin-induced diabetes mellitus in rats. Circulation 93, 1905-1912Google Scholar
76Asif, M. et al. (2000) An advanced glycation endproduct cross-link breaker can reverse age-related increases in myocardial stiffness. Proceedings of the National Academy of Sciences of the United States of America 97, 2809-2813Google Scholar
77Little, W.C. et al. (2005) The effect of alagebrium chloride (ALT-711), a novel glucose cross-link breaker, in the treatment of elderly patients with diastolic heart failure. Journal of Cardiac Failure 11, 191-195Google Scholar
78Thohan, V. et al. (2005) Improvements in diastolic function among patients with advanced systolic heart failure utilizing alagebrium (an oral advanced glycation end-product cross-link breaker). Circulation 112, 2620-2647Google Scholar
79Liu, J. et al. (2003) Glycation end-product cross-link breaker reduces collagen and improves cardiac function in aging diabetic heart. American Journal of Physiology – Heart and Circulatory Physiology 285, H2587-H2591CrossRefGoogle ScholarPubMed
80Vaitkevicius, M. et al. (2001) A cross-link breaker has sustained effects on arterial and ventricular properties in older rhesus monkeys. Proceedings of the National Academy of Sciences of the United States of America 98, 1171-1175CrossRefGoogle Scholar
81Cheng, G. et al. (2005) C16, a novel advanced glycation endproduct breaker, restores cardiovascular dysfunction in experimental diabetic rats. Acta Pharmacologica Sinica 26, 1460-1466Google Scholar
82Petrova, R. et al. (2002) Advanced glycation endproduct induced calcium handling impairment in mouse cardiac myocytes. Journal of Molecular and Cellular Cardiology 34, 1425-1431CrossRefGoogle ScholarPubMed
83Xie, J. et al. (2007) Hexameric calgranulin C (S100A12) binds to the receptor for advanced glycated end products (RAGE) using symmetric hydrophobic target-binding patches. Journal of Biological Chemistry 282, 4218-4231CrossRefGoogle Scholar
84Dattilo, B.M. et al. (2007) The extracellular region of the receptor for advanced glycation endproducts is composed of two independent structural units. Biochemistry 46, 6957-6970Google Scholar
85Leclerc, E. et al. (2007) S100b and S100A6 differentially modulate cell survival by interacting with distinct RAGE (receptor for advanced glycated end products) immunoglobulin domains. Journal of Biological Chemistry 282, 31317-31331CrossRefGoogle ScholarPubMed
86Limana, F. et al. (2005) Exogenous high-mobility group box 1 protein induces myocardial regeneration after infarction via enhanced cardiac c-Kit+ cell proliferation and differentiation. Circulation Research 97, 73-83Google Scholar
87Ramasamy, R., Yan, S.F. and Schmidt, A.M. (2008) Stopping the primal RAGE reaction in myocardial infarction: capturing adaptive responses to heal the heart? Circulation 117, 3165-3167CrossRefGoogle ScholarPubMed
88Moser, B. et al. (2007) Receptor for advanced glycation end products expression on T cells contributes to antigen-specific cellular expansion in vivo. Journal of Immunology 179, 8051-8058CrossRefGoogle Scholar
89Rong, L.L. et al. (2004) Antagonism of RAGE suppresses nerve regeneration. The FASEB Journal 18, 1812-1817Google Scholar
90Rong, L.L. et al. (2004) RAGE modulates peripheral nerve regeneration via recruitment of both inflammatory and axonal outgrowth pathways. The FASEB Journal 18, 1818-1825Google Scholar
91Goova, M.T. et al. (2001) Blockade of receptor for advanced glycation endproducts restores effective wound healing in diabetic mice. American Journal of Pathology 159, 5130525CrossRefGoogle ScholarPubMed

Further reading, resources and contacts

Yamagishi, S. et al. (2008) Agents that block advanced glycation end product (AGE)-RAGE (receptor for AGEs)-oxidative stress system: a novel therapeutic strategy for diabetic vascular complications. Expert Opinion on Investigational Drugs 17, 983-996CrossRefGoogle ScholarPubMed
Smit, A.J. et al. (2008) Advanced glycation end products in chronic heart failure. Annals of the New York Academy of Sciences 1126, 225-230Google Scholar