RANKL–OPG and RAGE modulation in vascular calcification and diabetes: novel targets for therapy

Diabetologia

Volumn 57, Issue 11, 2014, Pages 2251-2260

  Ndip, Agbor ^a,b,c,d   Wilkinson, Fiona L ^e   Jude, Edward B ^c,f   Boulton, Andrew J M ^a,c,g   Alexander, M Yvonne ^e,g  

^a MANCHESTER ROYAL INFIRMARY   (United Kingdom)

^b WARRINGTON AND HALTON HOSPITALS NHS FOUNDATION TRUST   (United Kingdom)

^c UNIVERSITY OF MANCHESTER   (United Kingdom)

^d Manchester Diabetes Centre   (United Kingdom)

^e MANCHESTER METROPOLITAN UNIVERSITY   (United Kingdom)

^f TAMESIDE GENERAL HOSPITAL   (United Kingdom)

^g UNIVERSITY OF MANCHESTER   (United Kingdom)

Author keywords

AGE; Charcot neuroarthropathy; Diabetes; OPG; RAGE; RANKL; Review; Vascular calcification

Indexed keywords

GLUCOSE; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; OSTEOCALCIN; OSTEOCLAST DIFFERENTIATION FACTOR; OSTEOPROTEGERIN; ADVANCED GLYCOSYLATION END-PRODUCT RECEPTOR; IMMUNOGLOBULIN RECEPTOR;

ADVENTITIA; ATHEROSCLEROSIS; BLOOD VESSEL CALCIFICATION; CARDIOVASCULAR DISEASE; CORONARY ARTERY CALCIFICATION; DIABETES MELLITUS; DIABETIC PATIENT; HUMAN; MORBIDITY; MORTALITY; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; REVIEW; SMOOTH MUSCLE FIBER; VASCULARIZATION; ANIMAL; METABOLISM; PHYSIOLOGY; SIGNAL TRANSDUCTION;

ANIMALS; DIABETES MELLITUS, TYPE 2; HUMANS; OSTEOPROTEGERIN; RANK LIGAND; RECEPTORS, IMMUNOLOGIC; SIGNAL TRANSDUCTION; VASCULAR CALCIFICATION;

EID: 84920003231     PISSN: 0012186X     EISSN: 14320428     Source Type: Journal    
DOI: 10.1007/s00125-014-3348-z     Document Type: Review

References (100)

1. King MR, Cooper GM, DeNevi D (2004) Who killed King Tut?: using modern forensics to solve a 3300-year-old mystery. Prometheus Books, Amherst
2. Allam AH, Thompson RC, Wann LS, Miyamoto MI, Thomas GS (2009) Computed tomographic assessment of atherosclerosis in ancient Egyptian mummies. JAMA J Am Med Assoc 302:2091–2094
3. Alexander MY, Wilkinson FL, Kirton JP et al (2005) Identification and characterization of vascular calcification-associated factor, a novel gene upregulated during vascular calcification in vitro and in vivo. Arterioscler Thromb Vasc Biol 25:1851–1857
4. Kirton JP, Wilkinson FL, Canfield AE, Alexander MY (2006) Dexamethasone downregulates calcification-inhibitor molecules and accelerates osteogenic differentiation of vascular pericytes: implications for vascular calcification. Circ Res 98:1264–1272
5. Liu Y, Wang T, Yan J et al (2011) HGF/c-Met signalling promotes Notch3 activation and human vascular smooth muscle cell osteogenic differentiation in vitro. Atherosclerosis 219:440–447
6. Ndip A, Williams A, Jude EB et al (2011) The RANKL/RANK/OPG signaling pathway mediates medial arterial calcification in diabetic Charcot neuroarthropathy. Diabetes 60:2187–2196
7. Wilkinson FL, Liu Y, Rucka AK et al (2007) Contribution of VCAF-positive cells to neovascularization and calcification in atherosclerotic plaque development. J Pathol 211:362–369
8. Yan J, Stringer SE, Hamilton A et al (2011) Decorin GAG synthesis and TGF-β signaling mediate Ox-LDL-induced mineralization of human vascular smooth muscle cells. Arterioscler Thromb Vasc Biol 31:608–615
9. Bostrom K, Watson KE, Horn S, Wortham C, Herman IM, Demer LL (1993) Bone morphogenetic protein expression in human atherosclerotic lesions. J Clin Invest 91:1800–1809
10. Bostrom KI, Rajamannan NM, Towler DA (2011) The regulation of valvular and vascular sclerosis by osteogenic morphogens. Circ Res 109:564–577
11. Giachelli CM, Speer MY, Li X, Rajachar RM, Yang H (2005) Regulation of vascular calcification: roles of phosphate and osteopontin. Circ Res 96:717–722
12. Proudfoot D, Shanahan CM (2006) Molecular mechanisms mediating vascular calcification: role of matrix Gla protein. Nephrology 11:455–461
13. Shanahan CM, Cary NR, Salisbury JR, Proudfoot D, Weissberg PL, Edmonds ME (1999) Medial localization of mineralization-regulating proteins in association with Monckeberg’s sclerosis: evidence for smooth muscle cell-mediated vascular calcification. Circulation 100:2168–2176
14. Steitz SA, Speer MY, Curinga G et al (2001) Smooth muscle cell phenotypic transition associated with calcification: upregulation of Cbfa1 and downregulation of smooth muscle lineage markers. Circ Res 89:1147–1154
15. Tintut Y, Alfonso Z, Saini T et al (2003) Multilineage potential of cells from the artery wall. Circulation 108:2505–2510
16. Towler DA, Shao JS, Cheng SL, Pingsterhaus JM, Loewy AP (2006) Osteogenic regulation of vascular calcification. Ann N Y Acad Sci 1068:327–333
17. Liu Y, Shanahan CM (2011) Signalling pathways and vascular calcification. Front Biosci 16:1302–1314
18. Rezg R, Barreto FC, Barreto DV, Liabeuf S, Drueke TB, Massy ZA (2011) Inhibitors of vascular calcification as potential therapeutic targets. J Nephrol 24:416–427
19. Sage AP, Tintut Y, Demer LL (2010) Regulatory mechanisms in vascular calcification. Nat Rev Cardiol 7:528–536
20. Hjortnaes J, New SE, Aikawa E (2013) Visualizing novel concepts of cardiovascular calcification. Trends Cardiovasc Med 23:71–79
21. Rogers M, Goettsch C, Aikawa E (2013) Medial and intimal calcification in chronic kidney disease: stressing the contributions. J Am Heart Assoc 2:e000481
22. Alexander MY, Heagerty AM, Keenan D (2008) Vascular calcification: characteristics and pathological mechanisms. In: Rowlands D, Clarke B (eds) Recent advances in cardiology, vol 15. Royal Society of Medicine Press, London, pp 21–43
23. Vattikuti R, Towler DA (2004) Osteogenic regulation of vascular calcification: an early perspective. Am J Physiol Endocrinol Metab 286:E686–E696
24. Proudfoot D, Shanahan CM (2001) Biology of calcification in vascular cells: intima versus media. Herz 26:245–251
25. Khavandgar Z, Roman H, Li J et al (2014) Elastin haploinsufficiency impedes the progression of arterial calcification in MGP-deficient mice. J Bone Miner Res 29:327–337
26. Pai A, Leaf EM, El-Abbadi M, Giachelli CM (2011) Elastin degradation and vascular smooth muscle cell phenotype change precede cell loss and arterial medial calcification in a uremic mouse model of chronic kidney disease. A J Pathol 178:764–773
27. Wang SS, Martin LJ, Schadt EE et al (2009) Disruption of the aortic elastic lamina and medial calcification share genetic determinants in mice. Circ Cardiovasc Genet 2:573–582
28. Reid DG, Shanahan CM, Duer MJ et al (2012) Lipids in biocalcification: contrasts and similarities between intimal and medial vascular calcification and bone by NMR. J Lipid Res 53:1569–1575
29. Shanahan CM, Crouthamel MH, Kapustin A, Giachelli CM (2011) Arterial calcification in chronic kidney disease: key roles for calcium and phosphate. Circ Res 109:697–711
30. Chen NX, Moe SM (2003) Arterial calcification in diabetes. Curr Diabetes Rep 3:28–32
31. Costacou T, Huskey ND, Edmundowicz D, Stolk R, Orchard TJ (2006) Lower-extremity arterial calcification as a correlate of coronary artery calcification. Metab Clin Exp 55:1689–1696
32. Young MJ, Adams JE, Anderson GF, Boulton AJ, Cavanagh PR (1993) Medial arterial calcification in the feet of diabetic patients and matched non-diabetic control subjects. Diabetologia 36:615–621
33. Jeffcoate W (2004) Vascular calcification and osteolysis in diabetic neuropathy-is RANK-L the missing link? Diabetologia 47:1488–1492
34. Chandra S, Rajamannan NM, Sucosky P (2012) Computational assessment of bicuspid aortic valve wall-shear stress: implications for calcific aortic valve disease. Biomech Model Mechanobiol 11:1085–1096
35. Brandenburg VM, Sinha S, Specht P, Ketteler M (2014) Calcific uraemic arteriolopathy: a rare disease with a potentially high impact on chronic kidney disease-mineral and bone disorder. Pediatr Nephrol. doi:10.1007/s00467-013-2746-7
36. Hofmann Bowman MA, McNally EM (2012) Genetic pathways of vascular calcification. Trends Cardiovasc Med 22:93–98
37. St Hilaire C, Ziegler SG, Markello TC et al (2011) NT5E mutations and arterial calcifications. N Engl J Med 364:432–442
38. Huang CC, Lloyd-Jones DM, Guo X et al (2011) Gene expression variation between African Americans and whites is associated with coronary artery calcification: the multiethnic study of atherosclerosis. Physiol Genomics 43:836–843
39. Jude EB, Selby PL, Burgess J et al (2001) Bisphosphonates in the treatment of Charcot neuroarthropathy: a double-blind randomised controlled trial. Diabetologia 44:2032–2037
40. Hessle L, Johnson KA, Anderson HC et al (2002) Tissue-nonspecific alkaline phosphatase and plasma cell membrane glycoprotein-1 are central antagonistic regulators of bone mineralization. Proc Natl Acad Sci U S A 99:9445–9449
41. Acharya A, Hans CP, Koenig SN et al (2011) Inhibitory role of Notch1 in calcific aortic valve disease. PLoS One 6:e27743
42. Garg V (2006) Molecular genetics of aortic valve disease. Curr Opin Cardiol 21:180–184
43. Shimizu T, Tanaka T, Iso T et al (2011) Notch signaling pathway enhances bone morphogenetic protein 2 (BMP2) responsiveness of Msx2 gene to induce osteogenic differentiation and mineralization of vascular smooth muscle cells. J Biol Chem 286:19138–19148
44. Yun YS, Choi SJ, Lee JY et al (2014) Impact of arterial microcalcification of the vascular access on cardiovascular mortality in hemodialysis patients. Hemodial Int Int Symp Home Hemodial 18:54–61
45. Blacher J, Guerin AP, Pannier B, Marchais SJ, London GM (2001) Arterial calcifications, arterial stiffness, and cardiovascular risk in end-stage renal disease. Hypertension 38:938–942
46. Maldonado N, Kelly-Arnold A, Vengrenyuk Y et al (2012) A mechanistic analysis of the role of microcalcifications in atherosclerotic plaque stability: potential implications for plaque rupture. Am J Physiol Heart Circ Physiol 303:H619–H628
47. Nicoll R, Henein MY (2013) Arterial calcification: friend or foe? Int J Cardiol 167:322–327
48. Steinberg DI (2012) ACP Journal Club. Novel risk markers improved Framingham Risk Score cardiovascular event prediction in intermediate-risk adults. Ann Intern Med 157:JC6–JC13
49. Lehto S, Niskanen L, Suhonen M, Ronnemaa T, Laakso M (1996) Medial artery calcification. A neglected harbinger of cardiovascular complications in non-insulin-dependent diabetes mellitus. Arterioscler Thromb Vasc Biol 16:978–983
50. Nelson RG, Gohdes DM, Everhart JE et al (1988) Lower-extremity amputations in NIDDM. 12-yr follow-up study in Pima Indians. Diabetes Care 11:8–16
51. Niskanen L, Siitonen O, Suhonen M, Uusitupa MI (1994) Medial artery calcification predicts cardiovascular mortality in patients with NIDDM. Diabetes Care 17:1252–1256
52. Carrington AL, Abbott CA, Griffiths J et al (2001) Peripheral vascular and nerve function associated with lower limb amputation in people with and without diabetes. Clin Sci 101:261–266
53. Alexander MY (2009) RANKL links arterial calcification with osteolysis. Circ Res 104:1032–1034
54. Mabilleau G, Petrova NL, Edmonds ME, Sabokbar A (2008) Increased osteoclastic activity in acute Charcot’s osteoarthropathy: the role of receptor activator of nuclear factor-κB ligand. Diabetologia 51:1035–1040
55. Rogers LC, Frykberg RG, Armstrong DG et al (2011) The Charcot foot in diabetes. J Am Podiatr Med Assoc 101:437–446
56. Panizo S, Cardus A, Encinas M et al (2009) RANKL increases vascular smooth muscle cell calcification through a RANK-BMP4-dependent pathway. Circ Res 104:1041–1048
57. Olesen M, Skov V, Mechta M, Mumm BH, Rasmussen LM (2012) No influence of OPG and its ligands, RANKL and TRAIL, on proliferation and regulation of the calcification process in primary human vascular smooth muscle cells. Mol Cell Endocrinol 362:149–156
58. Byon CH, Sun Y, Chen J et al (2011) Runx2-upregulated receptor activator of nuclear factor κB ligand in calcifying smooth muscle cells promotes migration and osteoclastic differentiation of macrophages. Arterioscler Thromb Vasc Biol 31:1387–1396
59. Browner WS, Lui LY, Cummings SR (2001) Associations of serum osteoprotegerin levels with diabetes, stroke, bone density, fractures, and mortality in elderly women. J Clin Endocrinol Metab 86:631–637
60. Jono S, Ikari Y, Shioi A et al (2002) Serum osteoprotegerin levels are associated with the presence and severity of coronary artery disease. Circulation 106:1192–1194
61. Collin-Osdoby P (2004) Regulation of vascular calcification by osteoclast regulatory factors RANKL and osteoprotegerin. Circ Res 95:1046–1057
62. Hofbauer LC, Brueck CC, Shanahan CM, Schoppet M, Dobnig H (2007) Vascular calcification and osteoporosis—from clinical observation towards molecular understanding. Osteoporos Int 18:251–259
63. Rasmussen LM, Tarnow L, Hansen TK, Parving HH, Flyvbjerg A (2006) Plasma osteoprotegerin levels are associated with glycaemic status, systolic blood pressure, kidney function and cardiovascular morbidity in type 1 diabetic patients. Eur J Endocrinol Eur Fed Endocr Soc 154:75–81
64. Franceschi C, Bonafe M, Valensin S et al (2000) Inflamm-aging. An evolutionary perspective on immunosenescence. Ann N Y Acad Sci 908:244–254
65. Bucay N, Sarosi I, Dunstan CR et al (1998) Osteoprotegerin-deficient mice develop early onset osteoporosis and arterial calcification. Genes Dev 12:1260–1268
66. –/– mice. Arterioscler Thromb Vasc Biol 27:2589–2596
67. 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 274:31740–31749
68. Ramasamy R, Yan SF, Schmidt AM (2009) RAGE: therapeutic target and biomarker of the inflammatory response—the evidence mounts. J Leukoc Biol 86:505–512
69. Ren X, Shao H, Wei Q, Sun Z, Liu N (2009) Advanced glycation end-products enhance calcification in vascular smooth muscle cells. J Int Med Res 37:847–854
70. ε-carboxymethyl-lysine accelerates progression of atherosclerotic calcification in diabetes. Atherosclerosis 221:387–396
71. Tanikawa T, Okada Y, Tanikawa R, Tanaka Y (2009) Advanced glycation end products induce calcification of vascular smooth muscle cells through RAGE/p38 MAPK. J Vasc Res 46:572–580
72. Giacco F, Brownlee M (2010) Oxidative stress and diabetic complications. Circ Res 107:1058–1070
73. Manigrasso MB, Juranek J, Ramasamy R, Schmidt AM (2014) Unlocking the biology of RAGE in diabetic microvascular complications. Trends Endocrinol Metab TEM 25:15–22
74. Hermann A, Donato R, Weiger TM, Chazin WJ (2012) S100 calcium binding proteins and ion channels. Front Pharmacol 3:67
75. Sima AV, Botez GM, Stancu CS, Manea A, Raicu M, Simionescu M (2010) Effect of irreversibly glycated LDL in human vascular smooth muscle cells: lipid loading, oxidative and inflammatory stress. J Cell Mol Med 14:2790–2802
76. Donato R (2001) S100: a multigenic family of calcium-modulated proteins of the EF-hand type with intracellular and extracellular functional roles. Int J Biochem Cell Biol 33:637–668
77. Tam XH, Shiu SW, Leng L, Bucala R, Betteridge DJ, Tan KC (2011) Enhanced expression of receptor for advanced glycation end-products is associated with low circulating soluble isoforms of the receptor in type 2 diabetes. Clin Sci 120:81–89
78. Yan SF, Ramasamy R, Schmidt AM (2010) The RAGE axis: a fundamental mechanism signaling danger to the vulnerable vasculature. Circ Res 106:842–853
79. Cecil DL, Terkeltaub RA (2011) Arterial calcification is driven by RAGE in Enpp1-/- mice. J Vasc Res 48:227–235
80. Hofmann Bowman MA, Gawdzik J, Bukhari U et al (2011) S100A12 in vascular smooth muscle accelerates vascular calcification in apolipoprotein E-null mice by activating an osteogenic gene regulatory program. Arterioscler Thromb Vasc Biol 31:337–344
81. Byon CH, Javed A, Dai Q et al (2008) Oxidative stress induces vascular calcification through modulation of the osteogenic transcription factor Runx2 by AKT signaling. J Biol Chem 283:15319–15327
82. Arumugam T, Ramachandran V, Gomez SB, Schmidt AM, Logsdon CD (2012) S100P-derived RAGE antagonistic peptide reduces tumor growth and metastasis. Clin Cancer Res Off J Am Assoc Cancer Res 18:4356–4364
83. Towler DA (2011) Vascular calcification: it’s all the RAGE! Arterioscler Thromb Vasc Biol 31:237–239
84. Yoshida T, Flegler A, Kozlov A, Stern PH (2009) Direct inhibitory and indirect stimulatory effects of RAGE ligand S100 on sRANKL-induced osteoclastogenesis. J Cell Biochem 107:917–925
85. Franke S, Siggelkow H, Wolf G, Hein G (2007) Advanced glycation endproducts influence the mRNA expression of RAGE, RANKL and various osteoblastic genes in human osteoblasts. Arch Physiol Biochem 113:154–161
86. Chalk C, Benstead TJ, Moore F (2007) Aldose reductase inhibitors for the treatment of diabetic polyneuropathy. Cochrane Database Syst Rev (4), Art. no.: CD004572. doi:10.1002/14651858.CD004572.pub2
87. Chang PC, Chong LY, Tsai SC, Lim LP (2014) Aminoguanidine inhibits the AGE–RAGE axis to modulate the induction of periodontitis but has limited effects on the progression and recovery of experimental periodontitis: a preliminary study. J Periodontol 85:729–739
88. Williams ME, Bolton WK, Khalifah RG, Degenhardt TP, Schotzinger RJ, McGill JB (2007) Effects of pyridoxamine in combined phase 2 studies of patients with type 1 and type 2 diabetes and overt nephropathy. Am J Nephrol 27:605–614
89. Witzke KA, Vinik AI, Grant LM et al (2011) Loss of RAGE defense: a cause of Charcot neuroarthropathy? Diabetes Care 34:1617–1621
90. Goova MT, Li J, Kislinger T et al (2001) Blockade of receptor for advanced glycation end-products restores effective wound healing in diabetic mice. Am J Pathol 159:513–525
91. 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
92. Lalla E, Lamster IB, Hofmann MA et al (2003) Oral infection with a periodontal pathogen accelerates early atherosclerosis in apolipoprotein E-null mice. Arterioscler Thromb Vasc Biol 23:1405–1411
93. Motyl K, McCabe LR (2009) Streptozotocin, type I diabetes severity and bone. Biol Proced Online 11:296–315
94. UK Prospective Diabetes Study (UKPDS) Group. (1998) Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet 352:854–865
95. Duckworth W, Abraira C, Moritz T et al (2009) Glucose control and vascular complications in veterans with type 2 diabetes. N Engl J Med 360:129–139
96. Group AC, Patel A, MacMahon S et al (2008) Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med 358:2560–2572
97. Action to Control Cardiovascular Risk in Diabetes Study G, Gerstein HC, Miller ME et al (2008) Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med 358:2545–2559
98. Katakami N, Kaneto H, Shimomura I (2014) Carotid ultrasonography: a potent tool for better clinical practice in diagnosis of atherosclerosis in diabetic patients. J Diabetes Investig 5:3–13
99. Polonsky TS, McClelland RL, Jorgensen NW et al (2010) Coronary artery calcium score and risk classification for coronary heart disease prediction. JAMA J Am Med Assoc 303:1610–1616
100. Schurgin S, Rich S, Mazzone T (2001) Increased prevalence of significant coronary artery calcification in patients with diabetes. Diabetes Care 24:335–338