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The receptor for advanced glycation end products and acute lung injury/acute respiratory distress syndrome

Weidun Alan Guo| Paul R. Knight| Krishnan Raghavendran
Review
Volume 38, Issue 10 / October , 2012

Pages 1588 - 1598

Abstract

The receptor for advanced glycation end products (RAGE) is a pattern-recognition receptor and evolutionary member of the immunoglobulin superfamily that is involved in the host response to infection, injury, and inflammation. It exists in two forms: membrane-bound and soluble forms (sRAGE). RAGE recognizes a variety of ligands and, via a receptor-driven signaling cascade, activates the transcription factor NF-κB, leading to the expression of proinflammatory cytokines. The soluble form, sRAGE, is a decoy receptor and competitively inhibits membrane RAGE activation. RAGE is constitutively expressed abundantly in the lung under basal conditions. This expression is enhanced during inflammatory states such as with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). This review summarizes the characteristics of RAGE, RAGE isoforms, RAGE ligands, and signaling pathways in the pathogenesis of ALI and ARDS. Additionally, the review explores the potential of RAGE as an important therapeutic target in ALI/ARDS.

Keywords

References

  1. Bernard GR, Artigas A, Brigham KL, Carlet J, Falke K, Hudson L, Lamy M, LeGall JR, Morris A, Spragg R (1994) Report of the American-European Consensus conference on acute respiratory distress syndrome: definitions, mechanisms, relevant outcomes, and clinical trial coordination. Consensus Committee. J Crit Care 9:72–81
    • View reference on PubMed
    • View reference on publisher's website
  2. Johnson ER, Matthay MA (2010) Acute lung injury: epidemiology, pathogenesis, and treatment. J Aerosol Med Pulm Drug Deliv 23:243–252
    • View reference on PubMed
    • View reference on publisher's website
  3. Ware LB, Matthay MA (2001) Alveolar fluid clearance is impaired in the majority of patients with acute lung injury and the acute respiratory distress syndrome. Am J Respir Crit Care Med 163:1376–1383
    • View reference on PubMed
  4. Johnson MD, Widdicombe JH, Allen L, Barbry P, Dobbs LG (2002) Alveolar epithelial type I cells contain transport proteins and transport sodium, supporting an active role for type I cells in regulation of lung liquid homeostasis. Proc Natl Acad Sci USA 99:1966–1971
    • View reference on PubMed
    • View reference on publisher's website
  5. Newman V, Gonzalez RF, Matthay MA, Dobbs LG (2000) A novel alveolar type I cell-specific biochemical marker of human acute lung injury. Am J Respir Crit Care Med 161:990–995
    • View reference on PubMed
  6. Shirasawa M, Fujiwara N, Hirabayashi S, Ohno H, Iida J, Makita K, Hata Y (2004) Receptor for advanced glycation end-products is a marker of type I lung alveolar cells. Genes Cells 9:165–174
    • View reference on PubMed
    • View reference on publisher's website
  7. Neeper M, Schmidt AM, Brett J, Yan SD, Wang F, Pan YC, Elliston K, Stern D, Shaw A (1992) Cloning and expression of a cell surface receptor for advanced glycosylation end products of proteins. J Biol Chem 267:14998–15004
    • View reference on PubMed
  8. Thornalley PJ (2003) The enzymatic defence against glycation in health, disease and therapeutics: a symposium to examine the concept. Biochem Soc Trans 31:1341–1342
    • View reference on PubMed
    • View reference on publisher's website
  9. Yan SF, Barile GR, D’Agati V, Du Yan S, Ramasamy R, Schmidt AM (2007) The biology of RAGE and its ligands: uncovering mechanisms at the heart of diabetes and its complications. Curr DiabRep 7:146–153
    • View reference on publisher's website
  10. Schmidt AM, Yan SD, Yan SF, Stern DM (2001) The multiligand receptor RAGE as a progression factor amplifying immune and inflammatory responses. J Clin Invest 108:949–955
    • View reference on PubMed
  11. Taguchi A, Blood DC, del Toro G, Canet A, Lee DC, Qu W, Tanji N, Lu Y, Lalla E, Fu C, Hofmann MA, Kislinger T, Ingram M, Lu A, Tanaka H, Hori O, Ogawa S, Stern DM, Schmidt AM (2000) Blockade of RAGE-amphoterin signalling suppresses tumour growth and metastases. Nature 405:354–360
    • View reference on PubMed
    • View reference on publisher's website
  12. Hofmann MA, Drury S, Fu C, Qu W, Taguchi A, Lu Y, Avila C, Kambham N, Bierhaus A, Nawroth P, Neurath MF, Slattery T, Beach D, McClary J, Nagashima M, Morser J, Stern D, Schmidt AM (1999) RAGE mediates a novel proinflammatory axis: a central cell surface receptor for S100/calgranulin polypeptides. Cell 97:889–901
    • View reference on PubMed
    • View reference on publisher's website
  13. Yamamoto Y, Harashima A, Saito H, Tsuneyama K, Munesue S, Motoyoshi S, Han D, Watanabe T, Asano M, Takasawa S, Okamoto H, Shimura S, Karasawa T, Yonekura H, Yamamoto H (2011) Septic shock is associated with receptor for advanced glycation end products ligation of LPS. J Immunol 186:3248–3257
    • View reference on PubMed
    • View reference on publisher's website
  14. He M, Kubo H, Morimoto K, Fujino N, Suzuki T, Takahasi T, Yamada M, Yamaya M, Maekawa T, Yamamoto Y, Yamamoto H (2011) Receptor for advanced glycation end products binds to phosphatidylserine and assists in the clearance of apoptotic cells. EMBO Rep 12:358–364
    • View reference on PubMed
    • View reference on publisher's website
  15. Bierhaus A, Schiekofer S, Schwaninger M, Andrassy M, Humpert PM, Chen J, Hong M, Luther T, Henle T, Kloting I, Morcos M, Hofmann M, Tritschler H, Weigle B, Kasper M, Smith M, Perry G, Schmidt AM, Stern DM, Haring HU, Schleicher E, Nawroth PP (2001) Diabetes-associated sustained activation of the transcription factor nuclear factor-kappaB. Diabetes 50:2792–2808
    • View reference on PubMed
    • View reference on publisher's website
  16. Aleshin A, Ananthakrishnan R, Li Q, Rosario R, Lu Y, Qu W, Song F, Bakr S, Szabolcs M, D’Agati V, Liu R, Homma S, Schmidt AM, Yan SF, Ramasamy R (2008) RAGE modulates myocardial injury consequent to LAD infarction via impact on JNK and STAT signaling in a murine model. Am J Physiol Heart Circ Physiol 294:H1823–H1832
    • View reference on PubMed
    • View reference on publisher's website
  17. van Beijnum JR, Buurman WA, Griffioen AW (2008) Convergence and amplification of toll-like receptor (TLR) and receptor for advanced glycation end products (RAGE) signaling pathways via high mobility group B1 (HMGB1). Angiogenesis 11:91–99
    • View reference on PubMed
    • View reference on publisher's website
  18. Janeway CA Jr, Medzhitov R (2002) Innate immune recognition. Annu Rev Immunol 20:197–216
    • View reference on PubMed
    • View reference on publisher's website
  19. Natarajan B, Gupta PK, Cemaj S, Sorensen M, Hatzoudis GI, Forse RA (2010) FAST scan: is it worth doing in hemodynamically stable blunt trauma patients? Surgery 148:695–700 (discussion 700–691)
    • View reference on PubMed
    • View reference on publisher's website
  20. Scaffidi P, Misteli T, Bianchi ME (2002) Release of chromatin protein HMGB1 by necrotic cells triggers inflammation. Nature 418:191–195
    • View reference on PubMed
    • View reference on publisher's website
  21. Bianchi R, Adami C, Giambanco I, Donato R (2007) S100B binding to RAGE in microglia stimulates COX-2 expression. J Leukoc Biol 81:108–118
    • View reference on PubMed
    • View reference on publisher's website
  22. Kuipers MT, van der Poll T, Schultz MJ, Wieland CW (2011) Bench-to-bedside review: damage-associated molecular patterns in the onset of ventilator-induced lung injury. Crit Care 15:235
    • View reference on PubMed
    • View reference on publisher's website
  23. Zhang Q, Raoof M, Chen Y, Sumi Y, Sursal T, Junger W, Brohi K, Itagaki K, Hauser CJ (2010) Circulating mitochondrial DAMPs cause inflammatory responses to injury. Nature 464:U104–U115
    • View reference on publisher's website
  24. Harris HE, Raucci A (2006) Alarmin(g) news about danger: workshop on innate danger signals and HMGB1. EMBO Rep 7:774–778
    • View reference on PubMed
  25. Tian J, Avalos AM, Mao SY, Chen B, Senthil K, Wu H, Parroche P, Drabic S, Golenbock D, Sirois C, Hua J, An LL, Audoly L, La Rosa G, Bierhaus A, Naworth P, Marshak-Rothstein A, Crow MK, Fitzgerald KA, Latz E, Kiener PA, Coyle AJ (2007) Toll-like receptor 9-dependent activation by DNA-containing immune complexes is mediated by HMGB1 and RAGE. Nat Immunol 8:487–496
    • View reference on PubMed
    • View reference on publisher's website
  26. Xiang M, Fan J (2010) Pattern recognition receptor-dependent mechanisms of acute lung injury. Mol Med (Cambridge, Mass) 16:69–82
  27. Schmidt AM, Yan SD, Yan SF, Stern DM (2000) The biology of the receptor for advanced glycation end products and its ligands. Biochim Biophys Acta 1498:99–111
    • View reference on PubMed
    • View reference on publisher's website
  28. Chavakis T, Bierhaus A, Nawroth PP (2004) RAGE (receptor for advanced glycation end products): a central player in the inflammatory response. Microbes Infect 6:1219–1225
    • View reference on PubMed
    • View reference on publisher's website
  29. Bierhaus A, Humpert PM, Morcos M, Wendt T, Chavakis T, Arnold B, Stern DM, Nawroth PP (2005) Understanding RAGE, the receptor for advanced glycation end products. J Mol Med (Berlin, Germany) 83:876–886
    • View reference on publisher's website
  30. Brett J, Schmidt AM, Yan SD, Zou YS, Weidman E, Pinsky D, Nowygrod R, Neeper M, Przysiecki C, Shaw A et al (1993) Survey of the distribution of a newly characterized receptor for advanced glycation end products in tissues. Am J Pathol 143:1699–1712
    • View reference on PubMed
  31. Hanford LE, Fattman CL, Shaefer LM, Enghild JJ, Valnickova Z, Oury TD (2003) Regulation of receptor for advanced glycation end products during bleomycin-induced lung injury. Am J Respir Cell Mol Biol 29:S77–S81
    • View reference on PubMed
  32. Hanford LE, Enghild JJ, Valnickova Z, Petersen SV, Schaefer LM, Schaefer TM, Reinhart TA, Oury TD (2004) Purification and characterization of mouse soluble receptor for advanced glycation end products (sRAGE). J Biol Chem 279:50019–50024
    • View reference on PubMed
    • View reference on publisher's website
  33. Englert JM, Hanford LE, Kaminski N, Tobolewski JM, Tan RJ, Fattman CL, Ramsgaard L, Richards TJ, Loutaev I, Nawroth PP, Kasper M, Bierhaus A, Oury TD (2008) A role for the receptor for advanced glycation end products in idiopathic pulmonary fibrosis. Am J Pathol 172:583–591
    • View reference on PubMed
    • View reference on publisher's website
  34. McElroy MC, Kasper M (2004) The use of alveolar epithelial type I cell-selective markers to investigate lung injury and repair. Eur Respir J 24:664–673
    • View reference on PubMed
    • View reference on publisher's website
  35. Cheng C, Tsuneyama K, Kominami R, Shinohara H, Sakurai S, Yonekura H, Watanabe T, Takano Y, Yamamoto H, Yamamoto Y (2005) Expression profiling of endogenous secretory receptor for advanced glycation end products in human organs. Mod Pathol 18:1385–1396
    • View reference on PubMed
    • View reference on publisher's website
  36. Morbini P, Villa C, Campo I, Zorzetto M, Inghilleri S, Luisetti M (2006) The receptor for advanced glycation end products and its ligands: a new inflammatory pathway in lung disease? Mod Pathol 19:1437–1445
    • View reference on PubMed
  37. Demling N, Ehrhardt C, Kasper M, Laue M, Knels L, Rieber EP (2006) Promotion of cell adherence and spreading: a novel function of RAGE, the highly selective differentiation marker of human alveolar epithelial type I cells. Cell Tissue Res 323:475–488
    • View reference on PubMed
    • View reference on publisher's website
  38. Repapi E, Sayers I, Wain LV, Burton PR, Johnson T, Obeidat M, Zhao JH, Ramasamy A, Zhai G, Vitart V, Huffman JE, Igl W, Albrecht E, Deloukas P, Henderson J, Granell R, McArdle WL, Rudnicka AR, Barroso I, Loos RJ, Wareham NJ, Mustelin L, Rantanen T, Surakka I, Imboden M, Wichmann HE, Grkovic I, Jankovic S, Zgaga L, Hartikainen AL, Peltonen L, Gyllensten U, Johansson A, Zaboli G, Campbell H, Wild SH, Wilson JF, Glaser S, Homuth G, Volzke H, Mangino M, Soranzo N, Spector TD, Polasek O, Rudan I, Wright AF, Heliovaara M, Ripatti S, Pouta A, Naluai AT, Olin AC, Toren K, Cooper MN, James AL, Palmer LJ, Hingorani AD, Wannamethee SG, Whincup PH, Smith GD, Ebrahim S, McKeever TM, Pavord ID, MacLeod AK, Morris AD, Porteous DJ, Cooper C, Dennison E, Shaheen S, Karrasch S, Schnabel E, Schulz H, Grallert H, Bouatia-Naji N, Delplanque J, Froguel P, Blakey JD, Britton JR, Morris RW, Holloway JW, Lawlor DA, Hui J, Nyberg F, Jarvelin MR, Jackson C, Kahonen M, Kaprio J, Probst-Hensch NM, Koch B, Hayward C, Evans DM, Elliott P, Strachan DP, Hall IP, Tobin MD (2010) Genome-wide association study identifies five loci associated with lung function. Nat Genet 42:36–44
    • View reference on PubMed
    • View reference on publisher's website
  39. Hancock DB, Eijgelsheim M, Wilk JB, Gharib SA, Loehr LR, Marciante KD, Franceschini N, van Durme YM, Chen TH, Barr RG, Schabath MB, Couper DJ, Brusselle GG, Psaty BM, van Duijn CM, Rotter JI, Uitterlinden AG, Hofman A, Punjabi NM, Rivadeneira F, Morrison AC, Enright PL, North KE, Heckbert SR, Lumley T, Stricker BH, O’Connor GT, London SJ (2010) Meta-analyses of genome-wide association studies identify multiple loci associated with pulmonary function. Nat Genet 42:45–52
    • View reference on PubMed
    • View reference on publisher's website
  40. Frommhold D, Kamphues A, Hepper I, Pruenster M, Lukic IK, Socher I, Zablotskaya V, Buschmann K, Lange-Sperandio B, Schymeinsky J, Ryschich E, Poeschl J, Kupatt C, Nawroth PP, Moser M, Walzog B, Bierhaus A, Sperandio M (2010) RAGE and ICAM-1 cooperate in mediating leukocyte recruitment during acute inflammation in vivo. Blood 116:841–849
    • View reference on PubMed
    • View reference on publisher's website
  41. Raucci A, Cugusi S, Antonelli A, Barabino SM, Monti L, Bierhaus A, Reiss K, Saftig P, Bianchi ME (2008) A soluble form of the receptor for advanced glycation endproducts (RAGE) is produced by proteolytic cleavage of the membrane-bound form by the sheddase a disintegrin and metalloprotease 10 (ADAM10). FASEB J 22:3716–3727
    • View reference on PubMed
    • View reference on publisher's website
  42. Uchida T, Shirasawa M, Ware LB, Kojima K, Hata Y, Makita K, Mednick G, Matthay ZA, Matthay MA (2006) Receptor for advanced glycation end-products is a marker of type I cell injury in acute lung injury. Am J Respir Crit Care Med 173:1008–1015
    • View reference on PubMed
    • View reference on publisher's website
  43. Zhang H, Tasaka S, Shiraishi Y, Fukunaga K, Yamada W, Seki H, Ogawa Y, Miyamoto K, Nakano Y, Hasegawa N, Miyasho T, Maruyama I, Ishizaka A (2008) Role of soluble receptor for advanced glycation end products on endotoxin-induced lung injury. Am J Respir Crit Care Med 178:356–362
    • View reference on PubMed
    • View reference on publisher's website
  44. Su X, Looney MR, Gupta N, Matthay MA (2009) Receptor for advanced glycation end-products (RAGE) is an indicator of direct lung injury in models of experimental lung injury. Am J Physiol Lung Cell Mol Physiol 297:L1–L5
    • View reference on PubMed
    • View reference on publisher's website
  45. Jabaudon M, Futier E, Roszyk L, Chalus E, Guerin R, Petit A, Mrozek S, Perbet S, Cayot-Constantin S, Chartier C, Sapin V, Bazin JE, Constantin JM (2011) Soluble form of the receptor for advanced glycation end products is a marker of acute lung injury but not of severe sepsis in critically ill patients. Crit Care Med 39:480–488
    • View reference on PubMed
    • View reference on publisher's website
  46. Christie JD, Shah CV, Kawut SM, Mangalmurti N, Lederer DJ, Sonett JR, Ahya VN, Palmer SM, Wille K, Lama V, Shah PD, Shah A, Weinacker A, Deutschman CS, Kohl BA, Demissie E, Bellamy S, Ware LB (2009) Plasma levels of receptor for advanced glycation end products, blood transfusion, and risk of primary graft dysfunction. Am J Respir Crit Care Med 180:1010–1015
    • View reference on PubMed
    • View reference on publisher's website
  47. Cohen MJ, Carles M, Brohi K, Calfee CS, Rahn P, Call MS, Chesebro BB, West MA, Pittet JF (2010) Early release of soluble receptor for advanced glycation endproducts after severe trauma in humans. J Trauma 68:1273–1278
    • View reference on PubMed
    • View reference on publisher's website
  48. Calfee CS, Ware LB, Eisner MD, Parsons PE, Thompson BT, Wickersham N, Matthay MA (2008) Plasma receptor for advanced glycation end products and clinical outcomes in acute lung injury. Thorax 63:1083–1089
    • View reference on PubMed
    • View reference on publisher's website
  49. Gefter JV, Shaufl AL, Fink MP, Delude RL (2009) Comparison of distinct protein isoforms of the receptor for advanced glycation end-products expressed in murine tissues and cell lines. Cell Tissue Res 337:79–89
    • View reference on PubMed
    • View reference on publisher's website
  50. Mukherjee TK, Mukhopadhyay S, Hoidal JR (2008) Implication of receptor for advanced glycation end product (RAGE) in pulmonary health and pathophysiology. Respir Physiol Neurobiol 162:210–215
    • View reference on PubMed
    • View reference on publisher's website
  51. Foell D, Wittkowski H, Roth J (2007) Mechanisms of disease: a ‘DAMP’ view of inflammatory arthritis. Nat Clin Pract Rheumatol 3:382–390
    • View reference on PubMed
    • View reference on publisher's website
  52. Bucciarelli LG, Wendt T, Rong L, Lalla E, Hofmann MA, Goova MT, Taguchi A, Yan SF, Yan SD, Stern DM, Schmidt AM (2002) RAGE is a multiligand receptor of the immunoglobulin superfamily: implications for homeostasis and chronic disease. Cell Mol Life Sci 59:1117–1128
    • View reference on PubMed
    • View reference on publisher's website
  53. Ramasamy R, Vannucci SJ, Yan SS, Herold K, Yan SF, Schmidt AM (2005) Advanced glycation end products and RAGE: a common thread in aging, diabetes, neurodegeneration, and inflammation. Glycobiology 15:16R–28R
    • View reference on PubMed
    • View reference on publisher's website
  54. Ulrich P, Cerami A (2001) Protein glycation, diabetes, and aging. Recent Prog Horm Res 56:1–21
    • View reference on PubMed
    • View reference on publisher's website
  55. Vlassara H (2005) Advanced glycation in health and disease: role of the modern environment. Ann N Y Acad Sci 1043:452–460
    • View reference on PubMed
    • View reference on publisher's website
  56. Wang H, Vishnubhakat JM, Bloom O, Zhang M, Ombrellino M, Sama A, Tracey KJ (1999) Proinflammatory cytokines (tumor necrosis factor and interleukin 1) stimulate release of high mobility group protein-1 by pituicytes. Surgery 126:389–392
    • View reference on PubMed
    • View reference on publisher's website
  57. Tikellis C, Thomas MC, Harcourt BE, Coughlan MT, Pete J, Bialkowski K, Tan A, Bierhaus A, Cooper ME, Forbes JM (2008) Cardiac inflammation associated with a Western diet is mediated via activation of RAGE by AGEs. Am J Physiol Endocrinol Metab 295:E323–E330
    • View reference on PubMed
    • View reference on publisher's website
  58. Ottosen JM, Mullan B, Ohtake PJ, Davidson BA, Knight PR, Guo WA (2010) Diet high in advanced glycation end products exacerbates pulmonary inflammatory response and impairs lung compliance in mice following gastric aspiration. J Surg Res 158:214
    • View reference on publisher's website
  59. Leclerc E, Fritz G, Vetter SW, Heizmann CW (2009) Binding of S100 proteins to RAGE: an update. Biochim Biophys Acta 1793:993–1007
    • View reference on PubMed
    • View reference on publisher's website
  60. Foell D, Wittkowski H, Vogl T, Roth J (2007) S100 proteins expressed in phagocytes: a novel group of damage-associated molecular pattern molecules. J Leukoc Biol 81:28–37
    • View reference on PubMed
    • View reference on publisher's website
  61. Vogl T, Propper C, Hartmann M, Strey A, Strupat K, van den Bos C, Sorg C, Roth J (1999) S100A12 is expressed exclusively by granulocytes and acts independently from MRP8 and MRP14. J Biol Chem 274:25291–25296
    • View reference on PubMed
    • View reference on publisher's website
  62. Wittkowski H, Sturrock A, van Zoelen MA, Viemann D, van der Poll T, Hoidal JR, Roth J, Foell D (2007) Neutrophil-derived S100A12 in acute lung injury and respiratory distress syndrome. Crit Care Med 35:1369–1375
    • View reference on PubMed
    • View reference on publisher's website
  63. Kikkawa T, Sato N, Kojika M, Takahashi G, Aoki K, Hoshikawa K, Akitomi S, Shozushima T, Suzuki K, Wakabayashi G, Endo S (2010) Significance of measuring S100A12 and sRAGE in the serum of sepsis patients with postoperative acute lung injury. Dig Surg 27:307–312
    • View reference on PubMed
    • View reference on publisher's website
  64. Dumitriu IE, Baruah P, Manfredi AA, Bianchi ME, Rovere-Querini P (2005) HMGB1: guiding immunity from within. Trends Immunol 26:381–387
    • View reference on PubMed
    • View reference on publisher's website
  65. Fink MP (2007) Bench-to-bedside review: high-mobility group box 1 and critical illness. Crit Care 11:229
    • View reference on PubMed
    • View reference on publisher's website
  66. Abraham E, Arcaroli J, Carmody A, Wang H, Tracey KJ (2000) HMG-1 as a mediator of acute lung inflammation. J Immunol 165:2950–2954
    • View reference on PubMed
  67. Gibot S, Massin F, Cravoisy A, Barraud D, Nace L, Levy B, Bollaert PE (2007) High-mobility group box 1 protein plasma concentrations during septic shock. Intensive Care Med 33:1347–1353
  68. Cohen MJ, Brohi K, Calfee CS, Rahn P, Chesebro BB, Christiaans SC, Carles M, Howard M, Pittet JF (2009) Early release of high mobility group box nuclear protein 1 after severe trauma in humans: role of injury severity and tissue hypoperfusion. Crit Care 13:R174
    • View reference on PubMed
    • View reference on publisher's website
  69. van Zoelen MA, Ishizaka A, Wolthuls EK, Choi G, van der Poll T, Schultz MJ (2008) Pulmonary levels of high-mobility group box 1 during mechanical ventilation and ventilator-associated pneumonia. Shock 29:441–445
    • View reference on PubMed
  70. Chavakis T, Bierhaus A, Al-Fakhri N, Schneider D, Witte S, Linn T, Nagashima M, Morser J, Arnold B, Preissner KT, Nawroth PP (2003) The pattern recognition receptor (RAGE) is a counter receptor for leukocyte integrins: a novel pathway for inflammatory cell recruitment. J Exp Med 198:1507–1515
    • View reference on PubMed
    • View reference on publisher's website
  71. Guo Y, Lu M, Qian J, Cheng YL (2009) Alagebrium chloride protects the heart against oxidative stress in aging rats. J Gerontol A Biol Sci Med Sci 64:629–635
    • View reference on PubMed
    • View reference on publisher's website
  72. Kim JB, Song BW, Park S, Hwang KC, Cha BS, Jang Y, Lee HC, Lee MH (2010) Alagebrium chloride, a novel advanced glycation end-product cross linkage breaker, inhibits neointimal proliferation in a diabetic rat carotid balloon injury model. Korean Circ J 40:520–526
    • View reference on PubMed
    • View reference on publisher's website
  73. Sugimoto H, Grahovac G, Zeisberg M, Kalluri R (2007) Renal fibrosis and glomerulosclerosis in a new mouse model of diabetic nephropathy and its regression by bone morphogenic protein-7 and advanced glycation end product inhibitors. Diabetes 56:1825–1833
    • View reference on PubMed
    • View reference on publisher's website
  74. Gaens KH, Niessen PM, Rensen SS, Buurman WA, Greve JW, Driessen A, Wolfs MG, Hofker MH, Bloemen JG, Dejong CH, Stehouwer CD, Schalkwijk CG (2012) Endogenous formation of Nε-(carboxymethyl)lysine is increased in fatty livers and induces inflammatory markers in an in vitro model of hepatic steatosis. J Hepatol 56:647–655
  75. Lutterloh EC, Opal SM, Pittman DD, Keith JC Jr, Tan XY, Clancy BM, Palmer H, Milarski K, Sun Y, Palardy JE, Parejo NA, Kessimian N (2007) Inhibition of the RAGE products increases survival in experimental models of severe sepsis and systemic infection. Crit Care 11:R122
    • View reference on PubMed
    • View reference on publisher's website
  76. Christaki E, Opal SM, Keith JC Jr, Kessimian N, Palardy JE, Parejo NA, Tan XY, Piche-Nicholas N, Tchistiakova L, Vlasuk GP, Shields KM, Feldman JL, Lavallie ER, Arai M, Mounts W, Pittman DD (2011) A monoclonal antibody against RAGE alters gene expression and is protective in experimental models of sepsis and pneumococcal pneumonia. Shock 35:492–498
    • View reference on PubMed
    • View reference on publisher's website
  77. Park L, Raman KG, Lee KJ, Lu Y, Ferran LJ Jr, Chow WS, Stern D, Schmidt AM (1998) Suppression of accelerated diabetic atherosclerosis by the soluble receptor for advanced glycation endproducts. Nat Med 4:1025–1031
    • View reference on PubMed
    • View reference on publisher's website
  78. Wear-Maggitti K, Lee J, Conejero A, Schmidt AM, Grant R, Breitbart A (2004) Use of topical sRAGE in diabetic wounds increases neovascularization and granulation tissue formation. Ann Plast Surg 52:519–521 (discussion 522)
    • View reference on PubMed
    • View reference on publisher's website
  79. Goova MT, Li J, Kislinger T, Qu W, Lu Y, Bucciarelli LG, Nowygrod S, Wolf BM, Caliste X, Yan SF, Stern DM, Schmidt AM (2001) Blockade of receptor for advanced glycation end-products restores effective wound healing in diabetic mice. Am J Pathol 159:513–525
    • View reference on PubMed
    • View reference on publisher's website
  80. Mauri T, Masson S, Pradella A, Bellani G, Coppadoro A, Bombino M, Valentino S, Patroniti N, Mantovani A, Pesenti A, Latini R (2010) Elevated plasma and alveolar levels of soluble receptor for advanced glycation endproducts are associated with severity of lung dysfunction in ARDS patients. Tohoku J Exp Med 222:105–112
    • View reference on PubMed
    • View reference on publisher's website
  81. Determann RM, Royakkers AA, Haitsma JJ, Zhang H, Slutsky AS, Ranieri VM, Schultz MJ (2010) Plasma levels of surfactant protein D and KL-6 for evaluation of lung injury in critically ill mechanically ventilated patients. BMC Pulm Med 10:6
    • View reference on PubMed
    • View reference on publisher's website
  82. Briot R, Frank JA, Uchida T, Lee JW, Calfee CS, Matthay MA (2009) Elevated levels of the receptor for advanced glycation end products, a marker of alveolar epithelial type I cell injury, predict impaired alveolar fluid clearance in isolated perfused human lungs. Chest 135:269–275
    • View reference on PubMed
    • View reference on publisher's website

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