AGE and RAGE inhibitors in the treatment of diabetic retinopathy

Expert Review of Ophthalmology

Volumn 2, Issue 1, 2007, Pages 105-120

  Bhatwadekar, Ashay ^a   Stitt, Alan W ^a  

^a QUEEN'S UNIVERSITY BELFAST   (United Kingdom)

Author keywords

advanced glycation end products; diabetic retinopathy; receptor for advanced glycation end products

Indexed keywords

EID: 41849096928     PISSN: 17469899     EISSN: 17469902     Source Type: Journal    
DOI: 10.1586/17469899.2.1.105     Document Type: Article

References (158)

1. Wild S, Roglic G, Green A, Sicree R, King H. Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care 27 (5), 1047–1053 (2004).
2. Fong DS, Sharza M, Chen W et al. Vision loss among diabetics in a group model Health Maintenance Organization (HMO). Am. J. Ophthalmol. 133 (2), 236–241 (2002).
3. Marshall SM, Flyvbjerg A. Prevention and early detection of vascular complications of diabetes. Br. Med. J 333 (7566), 475–480 (2006).
4. American Diabetes Association: clinical practice recommendations 2002. Diabetes Care 25 (Suppl. 1), S1 –S147 (2002).
5. Fong DS, Aiello L, Gardner TW et al. Retinopathy in diabetes. Diabetes Care 27 (Suppl. 1), S84 –S87 (2004).
6. Klein BE, Davis MD, Segal P et al. Diabetic retinopathy. Assessment of severity and progression. Ophthalmology 91 (1), 10–17 (1984).
7. Stratton IM, Kohner EM, Aldington SJ et al. UKPDS 50: risk factors for incidence and progression of retinopathy in Type II diabetes over 6 years from diagnosis. Diabetologia 44 (2), 156–163 (2001).
8. Retinopathy and nephropathy in patients with Type 1 diabetes four years after a trial of intensive therapy. The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group. N. Engl. J. Med. 342 (6), 381–389 (2000).
9. Chowdhury TA, Hopkins D, Dodson PM, Vafidis GC. The role of serum lipids in exudative diabetic maculopathy: is there a place for lipid lowering therapy? Eye 16 (6), 689–693 (2002).
10. Petrovic V, Bhisitkul RB. Lasers and diabetic retinopathy: the art of gentle destruction. Diabetes Technol. Ther. 1 (2), 177–187 (1999).
11. Klein R, Klein BE, Moss SE. Epidemiology of proliferative diabetic retinopathy. Diabetes Care 15 (12), 1875–1891 (1992).
12. Frank RN. Diabetic retinopathy. N. Engl. J. Med. 350 (1), 48–58 (2004).
13. Engerman RL. Pathogenesis of diabetic retinopathy. Diabetes 38 (10), 1203–1206 (1989).
14. Tzekov R, Arden GB. The electroretinogram in diabetic retinopathy. Surv. Ophthalmol. 44 (1), 53–60 (1999).
15. Gardner TW, Antonetti DA, Barber AJ, LaNoue KF, Nakamura M. New insights into the pathophysiology of diabetic retinopathy: potential cell-specific therapeutic targets. Diabetes Technol. Ther. 2 (4), 601–608 (2000).
16. Schmetterer L, Wolzt M. Ocular blood flow and associated functional deviations in diabetic retinopathy. Diabetologia 42 (4), 387–405 (1999).
17. Antonetti DA, Lieth E, Barber AJ, Gardner TW. Molecular mechanisms of vascular permeability in diabetic retinopathy. Semin. Ophthalmol. 14 (4), 240–248 (1999).
18. Stitt AW, Anderson HR, Gardiner TA, Archer DB. Diabetic retinopathy: quantitative variation in capillary basement membrane thickening in arterial or venous environments. Br. J. Ophthalmol. 78 (2), 133–137 (1994).
19. vom Hagen F, Feng Y, Hillenbrand A et al. Early loss of arteriolar smooth muscle cells: more than just a pericyte loss in diabetic retinopathy. Exp. Clin. Endocrinol. Diabetes 113 (10), 573–576 (2005).
20. Stitt AW, Gardiner TA, Archer DB. Histological and ultrastructural investigation of retinal microaneurysm development in diabetic patients. Br. J. Ophthalmol. 79 (4), 362–367 (1995).
21. Tilton RG, Chang K, Pugliese G et al. Prevention of hemodynamlemma and vascular albumin filtration changes in diabetic rats by aldose reductase inhibitors. Diabetes 38 (10), 1258–1270 (1989).
22. A randomized trial of sorbinil, an aldose reductase inhibitor, in diabetic retinopathy. Sorbinil Retinopathy Trial Research Group. Arch. Ophthalmol. 108 (9), 1234–1244 (1990).
23. Sun W, Oates PJ, Coutcher JB, Gerhardinger C, Lorenzi M. A selective aldose reductase inhibitor of a new structural class prevents or reverses early retinal abnormalities in experimental diabetic retinopathy. Diabetes 55 (10), 2757–2762 (2006).
24. Curtis TM, Scholfield CN. The role of lipids and protein kinase Cs in the pathogenesis of diabetic retinopathy. Diabetes Metab. Res. Rev. 20 (1), 28–43 (2004).
25. Obrosova IG, Minchenko AG, Marinescu V et al. Antioxidants attenuate early upregulation of retinal vascular endothelial growth factor in streptozotocin-diabetic rats. Diabetologia 44 (9), 1102–1110 (2001).
26. Tooke J. Possible pathophysiological mechanisms for diabetic angiopathy in Type 2 diabetes. J. Diabetes Complications 14 (4), 197–200 (2000).
27. Miyata T, van Ypersele de Strihou C. Angiotensin II receptor blockers and angiotensin converting enzyme inhibitors: implication of radical scavenging and transition metal chelation in inhibition of advanced glycation end product formation. Arch. Biochem. Biophys. 419 (1), 50–54 (2003).
28. Aiello LP, Davis MD, Girach A for the PKC-DRS2 Group. Effect of ruboxistaurin on visual loss in patients with diabetic retinopathy. Ophthalmology 113 (12), 2221–2230 (2006).
29. Brownlee M. Biochemistry and molecular cell biology of diabetic complications. Nature 414 (6865), 813–820 (2001).
30. Hammes HP, Du X, Edelstein D et al. Benfotiamine blocks three major pathways of hyperglycemic damage and prevents experimental diabetic retinopathy. Nat. Med. 9 (3), 294–299 (2003).
31. Bucala R, Vlassara H. Advanced glycosylation end products in diabetic renal and vascular disease. Am. J. Kidney Dis. 26 (6), 875–888 (1995).
32. Vlassara H, Palace MR. Diabetes and advanced glycation endproducts. J. Intern. Med. 251 (2), 87–101 (2002).
33. Wautier JL, Guillausseau PJ. Advanced glycation end products, their receptors and diabetic angiopathy. Diabetes Metab. 27 (5 Pt 1), 535–542 (2001).
34. Stitt AW, Jenkins AJ, Cooper ME. Advanced glycation end products and diabetic complications. Expert Opin. Investig. Drugs 11 (9), 1205–1223 (2002).
35. Monnier VM, Kohn RR, Cerami A. Accelerated age-related browning of human collagen in diabetes mellitus. Proc. Natl Acad. Sci. USA 81 (2), 583–587 (1984).
36. Hammes HP, Alt A, Niwa T et al. Differential accumulation of advanced glycation end products in the course of diabetic retinopathy. Diabetologia 42 (6), 728–736 (1999).
37. Thornalley PJ. Dicarbonyl intermediates in the maillard reaction. Ann. NY Acad. Sci. 1043, 111–117 (2005).
38. Baynes JW. The role of AGEs in aging: causation or correlation. Exp. Gerontol. 36 (9), 1527–1537 (2001).
39. Kuhla B, Luth HJ, Haferburg D et al. Methylglyoxal, glyoxal, and their detoxification in Alzheimer's disease. Ann. NY Acad. Sci. 1043, 211–216 (2005).
40. Shinohara M, Thornalley PJ, Giardino I et al. Overexpression of glyoxalase-I in bovine endothelial cells inhibits intracellular advanced glycation endproduct formation and prevents hyperglycemia-induced increases in macromolecular endocytosis. J. Clin. Invest. 101 (5), 1142–1147 (1998).
41. Baynes JW, Thorpe SR. Glycoxidation and lipoxidation in atherogenesis. Free Radic. Biol. Med. 28 (12), 1708–1716 (2000).
42. Genuth S, Sun W, Cleary P et al. Glycation and carboxymethyllysine levels in skin collagen predict the risk of future 10-year progression of diabetic retinopathy and nephropathy in the Diabetes Control and Complications Trial and Epidemiology of Diabetes Interventions and Complications participants with Type 1 diabetes. Diabetes 54 (11), 3103–3111 (2005).
43. Fosmark DS, Torjesen PA, Kilhovd BK et al. Increased serum levels of the specific advanced glycation end product methylglyoxal-derived hydroimidazolone are associated with retinopathy in patients with Type 2 diabetes mellitus. Metabolism 55 (2), 232–236 (2006).
44. Nakamura N, Hasegawa G, Obayashi H et al. Increased concentration of pentosidine, an advanced glycation end product, and interleukin-6 in the vitreous of patients with proliferative diabetic retinopathy. Diabetes Res. Clin. Pract. 61 (2), 93–101 (2003).
45. Sugiyama S, Miyata T, Ueda Y et al. Plasma levels of pentosidine in diabetic patients: an advanced glycation end product. J. Am. Soc. Nephrol. 9 (9), 1681–1688 (1998).
46. Stitt AW, Li YM, Gardiner TA et al. Advanced glycation end products (AGEs) co-localize with AGE receptors in the retinal vasculature of diabetic and of AGE-infused rats. Am. J. Pathol. 150 (2), 523–531 (1997).
47. Stitt AW, Bhaduri T, McMullen CB, Gardiner TA, Archer DB. Advanced glycation end products induce blood–retinal barrier dysfunction in normoglycemic rats. Mol. Cell Biol. Res. Commun. 3 (6), 380–388 (2000).
48. Xu X, Li Z, Luo D et al. Exogenous advanced glycosylation end products induce diabetes-like vascular dysfunction in normal rats: a factor in diabetic retinopathy. Graefes Arch. Clin. Exp. Ophthalmol. 241 (1), 56–62 (2003).
49. Kobayashi T, Oku H, Komori A et al. Advanced glycation end products induce death of retinal neurons via activation of nitric oxide synthase. Exp. Eye Res. 81 (6), 647–654 (2005).
50. Lecleire-Collet A, Tessier LH, Massin P et al. Advanced glycation end products can induce glial reaction and neuronal degeneration in retinal explants. Br. J. Ophthalmol. 89 (12), 1631–1633 (2005).
51. Yao D, Taguchi T, Matsumura T et al. Methylglyoxal modification of mSin3A links glycolysis to angiopoietin-2 transcription. Cell 124 (2), 275–286 (2006).
52. Stitt AW, Anderson HR, Gardiner TA, Bailie JR, Archer DB. Receptor-mediated endocytosis and intracellular trafficking of insulin and low-density lipoprotein by retinal vascular endothelial cells. Invest. Ophthalmol. Vis. Sci. 35 (9), 3384–3392 (1994).
53. Stitt AW, Burke GA, Chen F, McMullen CB, Vlassara H. Advanced glycation end-product receptor interactions on microvascular cells occur within caveolin-rich membrane domains. Faseb. J. 14 (15), 2390–2392 (2000).
54. Chen BH, Jiang DY, Tang LS. Advanced glycation end-products induce apoptosis involving the signaling pathways of oxidative stress in bovine retinal pericytes. Life Sci. 79 (11), 1040–1048 (2006).
55. Denis U, Lecomte M, Paget C et al. Advanced glycation end-products induce apoptosis of bovine retinal pericytes in culture: involvement of diacylglycerol/ceramide production and oxidative stress induction. Free Radic. Biol. Med. 33 (2), 236–247 (2002).
56. Yamagishi S, Fujimori H, Yonekura H, Tanaka N, Yamamoto H. Advanced glycation endproducts accelerate calcification in microvascular pericytes. Biochem. Biophys. Res. Commun. 258 (2), 353–357 (1999).
57. Liu B, Bhat M, Padival AK, Smith DG, Nagaraj RH. Effect of dicarbonyl modification of fibronectin on retinal capillary pericytes. Invest. Ophthalmol. Vis. Sci. 45 (6), 1983–1995 (2004).
58. 2+]i signalling and contraction in retinal microvascular pericytes. Mol. Vis. 10, 996–1004 (2004).
59. Miller AG, Smith DG, Bhat M, Nagaraj RH. Glyoxalase I is critical for human retinal capillary pericyte survival under hyperglycemic conditions. J. Biol. Chem. 281 (17), 11864–11871 (2006).
60. Mamputu JC, Renier G. Signalling pathways involved in retinal endothelial cell proliferation induced by advanced glycation end products: inhibitory effect of gliclazide. Diabetes Obes. Metab. 6 (2), 95–103 (2004).
61. Chibber R, Molinatti PA, Rosatto N, Lambourne B, Kohner EM. Toxic action of advanced glycation end products on cultured retinal capillary pericytes and endothelial cells: relevance to diabetic retinopathy. Diabetologia 40 (2), 156–164 (1997).
62. Stitt AW, McGoldrick C, Rice-McCaldin A et al. Impaired retinal angiogenesis in diabetes: role of advanced glycation end products and galectin-3. Diabetes 54 (3), 785–794 (2005).
63. Padayatti PS, Jiang C, Glomb MA, Uchida K, Nagaraj RH. High concentrations of glucose induce synthesis of argpyrimidine in retinal endothelial cells. Curr. Eye Res. 23 (2), 106–115 (2001).
64. Moore TC, Moore JE, Kaji Y et al. The role of advanced glycation end products in retinal microvascular leukostasis. Invest. Ophthalmol. Vis. Sci. 44 (10), 4457–4464 (2003).
65. Lu M, Kuroki M, Amano S et al. Advanced glycation end products increase retinal vascular endothelial growth factor expression. J. Clin. Invest. 101 (6), 1219–1224 (1998).
66. Treins C, Giorgetti-Peraldi S, Murdaca J, Van Obberghen E. Regulation of vascular endothelial growth factor expression by advanced glycation end products. J. Biol. Chem. 276 (47), 43836–43841 (2001).
67. Gardiner TA, Anderson HR, Stitt AW. Inhibition of advanced glycation end-products protects against retinal capillary basement membrane expansion during long-term diabetes. J. Pathol. 201 (2), 328–333 (2003).
68. Kern TS, Engerman RL. Pharmacological inhibition of diabetic retinopathy: aminoguanidine and aspirin. Diabetes 50 (7), 1636–1642 (2001).
69. Du Y, Sarthy VP, Kern TS. Interaction between NO and COX pathways in retinal cells exposed to elevated glucose and retina of diabetic rats. Am. J. Physiol. Regul. Integr. Comp. Physiol. 287 (4), R735 –R741 (2004).
70. Bolton WK, Cattran DC, Williams ME et al. Randomized trial of an inhibitor of formation of advanced glycation end products in diabetic nephropathy. Am. J. Nephrol. 24 (1), 32–40 (2004).
71. Taguchi T, Sugiura M, Hamada Y, Miwa I. In vivo formation of a Schiff base of aminoguanidine with pyridoxal phosphate. Biochem. Pharmacol. 55 (10), 1667–1671 (1998).
72. Yu PH, Zuo DM. Aminoguanidine inhibits semicarbazide-sensitive amine oxidase activity: implications for advanced glycation and diabetic complications. Diabetologia 40 (11), 1243–1250 (1997).
73. Misko TP, Moore WM, Kasten TP et al. Selective inhibition of the inducible nitric oxide synthase by aminoguanidine. Eur. J. Pharmacol. 233 (1), 119–125 (1993).
74. Forbes JM, Soulis T, Thallas V et al. Renoprotective effects of a novel inhibitor of advanced glycation. Diabetologia 44 (1), 108–114 (2001).
75. Voziyan PA, Metz TO, Baynes JW, Hudson BG. A post-Amadori inhibitor pyridoxamine also inhibits chemical modification of proteins by scavenging carbonyl intermediates of carbohydrate and lipid degradation. J. Biol. Chem. 277 (5), 3397–3403 (2002).
76. Nagaraj RH, Sarkar P, Mally A et al. Effect of pyridoxamine on chemical modification of proteins by carbonyls in diabetic rats: characterization of a major product from the reaction of pyridoxamine and methylglyoxal. Arch. Biochem. Biophys. 402 (1), 110–119 (2002).
77. Kang Z, Li H, Li G, Yin D. Reaction of pyridoxamine with malondialdehyde: mechanism of inhibition of formation of advanced lipoxidation end-products. Amino Acids 30 (1), 55–61 (2006).
78. Stitt A, Gardiner TA, Alderson NL et al. The AGE inhibitor pyridoxamine inhibits development of retinopathy in experimental diabetes. Diabetes 51 (9), 2826–2832 (2002).
79. Alderson NL, Chachich ME, Youssef NN et al. The AGE inhibitor pyridoxamine inhibits lipemia and development of renal and vascular disease in Zucker obese rats. Kidney Int. 63 (6), 2123–2133 (2003).
80. Padival S, Nagaraj RH. Pyridoxamine inhibits maillard reactions in diabetic rat lenses. Ophthalmic Res. 38 (5), 294–302 (2006).
81. Khalifah RG, Chen Y, Wassenberg JJ. Post-Amadori AGE inhibition as a therapeutic target for diabetic complications: a rational approach to second-generation Amadorin design. Ann. NY Acad. Sci. 1043, 793–806 (2005).
82. Bakris GL, Bank AJ, Kass DA et al. Advanced glycation end-product cross-link breakers. A novel approach to cardiovascular pathologies related to the aging process. Am. J. Hypertens. 17 (12 Pt 2), 23S –30S (2004).
83. Kass DA, Shapiro EP, Kawaguchi M et al. Improved arterial compliance by a novel advanced glycation end-product crosslink breaker. Circulation 104 (13), 1464–1470 (2001).
84. Liu J, Masurekar MR, Vatner DE et al. Glycation end-product cross-link breaker reduces collagen and improves cardiac function in aging diabetic heart. Am. J. Physiol. Heart Circ. Physiol. 285 (6), H2587 –H2591 (2003).
85. Forbes JM, Yee LT, Thallas V et al. Advanced glycation end product interventions reduce diabetes-accelerated atherosclerosis. Diabetes 53 (7), 1813–1823 (2004).
86. Figarola JL, Scott S, Loera S et al. LR-90 a new advanced glycation endproduct inhibitor prevents progression of diabetic nephropathy in streptozotocin-diabetic rats. Diabetologia 46 (8), 1140–1152 (2003).
87. Miyata T, Ueda Y, Asahi K et al. Mechanism of the inhibitory effect of OPB-9195 [(+/-)-2-isopropylide nehydrazono-4-oxo-thiazolidin-5-yl acetanilide] on advanced glycation end product and advanced lipoxidation end product formation. J. Am. Soc. Nephrol. 11 (9), 1719–1725 (2000).
88. Tsuchida K, Makita Z, Yamagishi S et al. Suppression of transforming growth factor β and vascular endothelial growth factor in diabetic nephropathy in rats by a novel advanced glycation end product inhibitor, OPB-9195. Diabetologia 42 (5), 579–588 (1999).
89. Nakamura S, Makita Z, Ishikawa S et al. Progression of nephropathy in spontaneous diabetic rats is prevented by OPB-9195, a novel inhibitor of advanced glycation. Diabetes 46 (5), 895–899 (1997).
90. Seidler NW, Yeargans GS, Morgan TG. Carnosine disaggregates glycated α-crystallin: an in vitro study. Arch. Biochem. Biophys. 427 (1), 110–115 (2004).
91. Babizhayev MA, Deyev AI, Yermakova VN et al. Efficacy of N-acetylcarnosine in the treatment of cataracts. Drugs R D, 3 (2), 87–103 (2002).
92. Stitt AW, He C, Friedman S et al. Elevated AGE-modified ApoB in sera of euglycemic, normolipidemic patients with atherosclerosis: relationship to tissue AGEs. Mol. Med. 3 (9), 617–627 (1997).
93. Lu C, He JC, Cai W et al. Advanced glycation endproduct (AGE) receptor 1 is a negative regulator of the inflammatory response to AGE in mesangial cells. Proc. Natl Acad. Sci. USA 101 (32), 11767–11772 (2004).
94. Stitt AW, He C, Vlassara H. Characterization of the advanced glycation end-product receptor complex in human vascular endothelial cells. Biochem. Biophys. Res. Commun. 256 (3), 549–556 (1999).
95. Zhu W, Sano H, Nagai R et al. The role of galectin-3 in endocytosis of advanced glycation end products and modified low density lipoproteins. Biochem. Biophys. Res. Commun. 280 (4), 1183–1188 (2001).
96. Iacobini C, Amadio L, Oddi G et al. Role of galectin-3 in diabetic nephropathy. J. Am. Soc. Nephrol. 14 (8 Suppl. 3), S264 –S270 (2003).
97. Pugliese G, Pricci F, Iacobini C et al. Accelerated diabetic glomerulopathy in galectin-3/AGE receptor 3 knockout mice. Faseb. J. 15 (13), 2471–2479 (2001).
98. Iacobini C, Menini S, Oddi G et al. Galectin-3/AGE-receptor 3 knockout mice show accelerated AGE-induced glomerular injury: evidence for a protective role of galectin-3 as an AGE receptor. Faseb. J. 18 (14), 1773–1775 (2004).
99. Tamura Y, Adachi H, Osuga J et al. FEEL-1 and FEEL-2 are endocytic receptors for advanced glycation end products. J. Biol. Chem. 278 (15), 12613–12617 (2003).
100. Horiuchi S, Sakamoto Y, Sakai M. Scavenger receptors for oxidized and glycated proteins. Amino Acids 25 (3–4), 283–292 (2003).
101. Ohgami N, Nagai R, Ikemoto M et al. CD36, a member of class B scavenger receptor family, is a receptor for advanced glycation end products. Ann. NY Acad. Sci. 947, 350–355 (2001).
102. Unno Y, Sakai M, Sakamoto Y et al. Advanced glycation end products-modified proteins and oxidized LDL mediate down-regulation of leptin in mouse adipocytes via CD36. Biochem. Biophys. Res. Commun. 325 (1), 151–156 (2004).
103. Kuniyasu A, Ohgami N, Hayashi S et al. CD36-mediated endocytic uptake of advanced glycation end products (AGE) in mouse 3T3-L1 and human subcutaneous adipocytes. FEBS Lett. 537 (1–3), 85–90 (2003).
104. Neeper M, Schmidt AM, Brett J et al. Cloning and expression of a cell surface receptor for advanced glycosylation end products of proteins. J. Biol. Chem. 267 (21), 14998–15004 (1992).
105. Brett J, Schmidt AM, Yan SD et al. Survey of the distribution of a newly characterized receptor for advanced glycation end products in tissues. Am. J. Pathol. 143 (6), 1699–1712 (1993).
106. Goldin A, Beckman JA, Schmidt AM, Creager MA. Advanced glycation end products: sparking the development of diabetic vascular injury. Circulation 114 (6), 597–605 (2006).
107. Hudson BI, Stickland MH, Futers TS, Grant PJ. Effects of novel polymorphisms in the RAGE gene on transcriptional regulation and their association with diabetic retinopathy. Diabetes 50 (6), 1505–1511 (2001).
108. Yonekura H, Yamamoto Y, Sakurai S et al. Novel splice variants of the receptor for advanced glycation end-products expressed in human vascular endothelial cells and pericytes, and their putative roles in diabetes-induced vascular injury. Biochem. J. 370 (Pt 3), 1097–1109 (2003).
109. Casselmann C, Reimann A, Friedrich I et al. Age-dependent expression of advanced glycation end product receptor genes in the human heart. Gerontology 50 (3), 127–134 (2004).
110. Kaji Y, Amano S, Usui T et al. Expression and function of receptors for advanced glycation end products in bovine corneal endothelial cells. Invest. Ophthalmol. Vis. Sci. 44 (2), 521–528 (2003).
111. Soulis T, Thallas V, Youssef S et al. Advanced glycation end products and their receptors co-localise in rat organs susceptible to diabetic microvascular injury. Diabetologia 40 (6), 619–628 (1997).
112. Hammes HP, Hoerauf H, Alt A et al. N(ε)(carboxymethyl)lysin and the AGE receptor RAGE colocalize in age-related macular degeneration. Invest. Ophthalmol. Vis. Sci. 40 (8), 1855–1859 (1999).
113. Howes KA, Liu Y, Dunaief JL et al. Receptor for advanced glycation end products and age-related macular degeneration. Invest. Ophthalmol. Vis. Sci. 45 (10), 3713–3720 (2004).
114. Barile GR, Pachydaki SI, Tari SR et al. The RAGE axis in early diabetic retinopathy. Invest. Ophthalmol. Vis. Sci. 46 (8), 2916–2924 (2005).
115. Kislinger T, Fu C, Huber B et al. N(ε)-(carboxymethyl)lysine adducts of proteins are ligands for receptor for advanced glycation end products that activate cell signaling pathways and modulate gene expression. J. Biol. Chem. 274 (44), 31740–31749 (1999).
116. Valencia JV, Weldon SC, Quinn D et al. Advanced glycation end product ligands for the receptor for advanced glycation end products: biochemical characterization and formation kinetics. Anal Biochem, 324 (1), 68–78 (2004).
117. Schmidt AM, Hori O, Chen JX et al. Advanced glycation endproducts interacting with their endothelial receptor induce expression of vascular cell adhesion molecule-1 (VCAM-1) in cultured human endothelial cells and in mice. A potential mechanism for the accelerated vasculopathy of diabetes. J. Clin. Invest. 96 (3), 1395–1403 (1995).
118. Wautier JL, Schmidt AM. Protein glycation: a firm link to endothelial cell dysfunction. Circ. Res. 95 (3), 233–238 (2004).
119. Lander HM, Tauras JM, Ogiste JS et al. Activation of the receptor for advanced glycation end products triggers a p21(ras)-dependent mitogen-activated protein kinase pathway regulated by oxidant stress. J. Biol. Chem. 272 (28), 17810–17814 (1997).
120. Yamagishi S, Fujimori H, Yonekura H, Yamamoto Y, Yamamoto H. Advanced glycation endproducts inhibit prostacyclin production and induce plasminogen activator inhibitor-1 in human microvascular endothelial cells. Diabetologia 41 (12), 1435–1441 (1998).
121. Shanmugam N, Kim YS, Lanting L, Natarajan R. Regulation of cyclooxygenase-2 expression in monocytes by ligation of the receptor for advanced glycation end products. J. Biol. Chem. 278 (37), 34834–34844 (2003).
122. Valencia JV, Mone M, Koehne C, Rediske J, Hughes TE. Binding of receptor for advanced glycation end products (RAGE) ligands is not sufficient to induce inflammatory signals: lack of activity of endotoxin-free albumin-derived advanced glycation end products. Diabetologia 47 (5), 844–852 (2004).
123. Collison KS, Parhar RS, Saleh SS et al. RAGE-mediated neutrophil dysfunction is evoked by advanced glycation end products (AGEs). J. Leukoc. Biol. 71 (3), 433–444 (2002).
124. Falcone C, Emanuele E, D'Angelo A et al. Plasma levels of soluble receptor for advanced glycation end products and coronary artery disease in nondiabetic men. Arterioscler. Thromb. Vasc. Biol. 25 (5), 1032–1037 (2005).
125. Katakami N, Matsuhisa M, Kaneto H et al. Decreased endogenous secretory advanced glycation end product receptor in Type 1 diabetic patients: its possible association with diabetic vascular complications. Diabetes Care 28 (11), 2716–2721 (2005).
126. Goova MT, Li J, Kislinger T et al. Blockade of receptor for advanced glycation end-products restores effective wound healing in diabetic mice. Am. J. Pathol. 159 (2), 513–525 (2001).
127. Pachydaki SI, Tari SR, Lee SE et al. Upregulation of RAGE and its ligands in proliferative retinal disease. Exp. Eye Res. 82 (5), 807–815 (2006).
128. Hori O, Brett J, Slattery T et al. The receptor for advanced glycation end products (RAGE) is a cellular binding site for amphoterin. Mediation of neurite outgrowth and co-expression of rage and amphoterin in the developing nervous system. J. Biol. Chem. 270 (43), 25752–25761 (1995).
129. Hofmann MA, Drury S, Fu C et al. RAGE mediates a novel proinflammatory axis: a central cell surface receptor for S100/calgranulin polypeptides. Cell 97 (7), 889–901 (1999).
130. Kosaki A, Hasegawa T, Kimura T et al. Increased plasma S100A12 (EN-RAGE) levels in patients with Type 2 diabetes. J. Clin. Endocrinol. Metab. 89 (11), 5423–5428 (2004).
131. Hasegawa T, Kosaki A, Kimura T et al. The regulation of EN-RAGE (S100A12) gene expression in human THP-1 macrophages. Atherosclerosis 171 (2), 211–218 (2003).
132. Kim MH, Choi YW, Choi HY, Myung KB, Cho SN. The expression of RAGE and EN-RAGE in leprosy. Br. J. Dermatol. 154 (4), 594–601 (2006).
133. Ehlermann P, Eggers K, Bierhaus A et al. Increased proinflammatory endothelial response to S100A8/A9 after preactivation through advanced glycation end products. Cardiovasc. Diabetol. 5, 6 (2006).
134. Zhou Z, Wang K, Penn MS et al. Receptor for AGE (RAGE) mediates neointimal formation in response to arterial injury. Circulation 107 (17), 2238–2243 (2003).
135. Taguchi A, Blood DC, del Toro G et al. Blockade of RAGE-amphoterin signalling suppresses tumour growth and metastases. Nature 405 (6784), 354–360 (2000).
136. Fiuza C, Bustin M, Talwar S et al. Inflammation-promoting activity of HMGB1 on human microvascular endothelial cells. Blood 101 (7), 2652–2660 (2003).
137. Rouhiainen A, Kuja-Panula J, Wilkman E et al. Regulation of monocyte migration by amphoterin (HMGB1). Blood 104 (4), 1174–1182 (2004).
138. Donahue JE, Flaherty SL, Johanson CE et al. RAGE, LRP-1, and amyloid-β protein in Alzheimer’s disease. Acta Neuropathol. (Berl.) 112 (4), 405–415 (2006).
139. Mruthinti S, Buccafusco JJ, Hill WD et al. Autoimmunity in Alzheimer's disease: increased levels of circulating IgGs binding Aβ and RAGE peptides. Neurobiol. Ageing 25 (8), 1023–1032 (2004).
140. Chaney MO, Stine WB, Kokjohn TA et al. RAGE and amyloid β interactions: atomic force microscopy and molecular modeling. Biochim. Biophys. Acta 1741 (1–2), 199–205 (2005).
141. Yan SD, Stern D, Kane MD et al. RAGE-Aβ interactions in the pathophysiology of Alzheimer’s disease. Restor. Neurol. Neurosci. 12 (2–3), 167–173 (1998).
142. Chavakis T, Bierhaus A, Al-Fakhri N et al. The pattern recognition receptor (RAGE) is a counterreceptor for leukocyte integrins: a novel pathway for inflammatory cell recruitment. J. Exp. Med. 198 (10), 1507–1515 (2003).
143. Yokoi M, Yamagishi SI, Takeuchi M et al. Elevations of AGE and vascular endothelial growth factor with decreased total antioxidant status in the vitreous fluid of diabetic patients with retinopathy. Br. J. Ophthalmol. 89 (6), 673–675 (2005).
144. Renard C, Chappey O, Wautier MP et al. Recombinant advanced glycation end product receptor pharmacokinetics in normal and diabetic rats. Mol. Pharmacol. 52 (1), 54–62 (1997).
145. Sakurai S, Yamamoto Y, Tamei H et al. Development of an ELISA for sRAGE and its application to Type 1 diabetic patients. Diabetes Res. Clin. Pract. 73 (2), 158–165 (2006).
146. Yamagishi S, Adachi H, Nakamura K et al. Positive association between serum levels of advanced glycation end products and the soluble form of receptor for advanced glycation end products in nondiabetic subjects. Metabolism 55 (9), 1227–1231 (2006).
147. Tan KC, Shiu SW, Chow WS et al. Association between serum levels of soluble receptor for advanced glycation end products and circulating advanced glycation end products in Type 2 diabetes. Diabetologia 49 (11), 2756–2762 (2006).
148. Miura J, Uchigata Y, Yamamoto Y et al. AGE down-regulation of monocyte RAGE expression and its association with diabetic complications in Type 1 diabetes. J. Diabetes Complications 18 (1), 53–59 (2004).
149. Hou FF, Ren H, Owen WF Jr et al. Enhanced expression of receptor for advanced glycation end products in chronic kidney disease. J. Am. Soc. Nephrol. 15 (7), 1889–1896 (2004).
150. Marx N, Walcher D, Ivanova N et al. Thiazolidinediones reduce endothelial expression of receptors for advanced glycation end products. Diabetes 53 (10), 2662–2668 (2004).
151. Yamagishi S, Takeuchi M. Nifedipine inhibits gene expression of receptor for advanced glycation end products (RAGE) in endothelial cells by suppressing reactive oxygen species generation. Drugs Exp. Clin. Res. 30 (4), 169–175 (2004).
152. Wang K, Zhou Z, Zhang M et al. Peroxisome proliferator-activated receptor γ down-regulates receptor for advanced glycation end products and inhibits smooth muscle cell proliferation in a diabetic and nondiabetic rat carotid artery injury model. J. Pharmacol. Exp. Ther. 317 (1), 37–43 (2006).
153. Yamagishi S, Nakamura K, Matsui T, Sato T, Takeuchi M. Potential utility of statins, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors in diabetic retinopathy. Med. Hypotheses 66 (5), 1019–1021 (2006).
154. Yamagishi S, Takeuchi M, Matsui T et al. Angiotensin II augments advanced glycation end product-induced pericyte apoptosis through RAGE overexpression. FEBS Lett. 579 (20), 4265–4270 (2005).
155. Koka V, Wang W, Huang XR et al. Advanced glycation end products activate a chymase-dependent angiotensin II-generating pathway in diabetic complications. Circulation 113 (10), 1353–1360 (2006).
156. Nakamura K, Yamagishi S, Nakamura Y et al. Telmisartan inhibits expression of a receptor for advanced glycation end products (RAGE) in angiotensin-II-exposed endothelial cells and decreases serum levels of soluble RAGE in patients with essential hypertension. Microvasc. Res. 70 (3), 137–141 (2005).
157. Stitt AW. The role of advanced glycation in the pathogenesis of diabetic retinopathy. Exp. Mol. Pathol. 75, 95–108 (2003).
158. Pfizer and TransTech Pharma enter into agreement for the development and commercialization of RAGE modulators. (TransTech Pharma Inc., 2006). www.ttpharma.com/press_releases/20061809_pfizer.html.