Seminars in Nephrology
Volume 27, Issue 2 , Pages 161-171 , March 2007

Angiogenesis in Diabetic Nephropathy

  • Roy Zent, MD, PhD
  • ,
  • Ambra Pozzi, PhD

      Affiliations

    • Corresponding Author InformationAddress reprint requests to Ambra Pozzi, PhD, Department of Medicine, Division of Nephrology, Vanderbilt University, Medical Center North, B3109, Nashville, TN, 37232.

References 

  1. Pandya NM, Dhalla NS, Santani DD. Angiogenesis—a new target for future therapy. Vascul Pharmacol. 2006;44:265–274
  2. Roy H, Bhardwaj S, Yla-Herttuala S. Biology of vascular endothelial growth factors. FEBS Lett. 2006;580:2879–2887
  3. Olsson AK, Dimberg A, Kreuger J, et al. VEGF receptor signalling—in control of vascular function. Nat Rev Mol Cell Biol. 2006;7:359–371
  4. Eklund L, Olsen BR. Tie receptors and their angiopoietin ligands are context-dependent regulators of vascular remodeling. Exp Cell Res. 2006;312:630–641
  5. Thurston G, Rudge JS, Ioffe E, et al. Angiopoietin-1 protects the adult vasculature against plasma leakage. Nat Med. 2000;6:460–463
  6. Thurston G, Suri C, Smith K, et al. Leakage-resistant blood vessels in mice transgenically overexpressing angiopoietin-1. Science. 1999;286:2511–2514
  7. Scharpfenecker M, Fiedler U, Reiss Y, et al. The Tie-2 ligand angiopoietin-2 destabilizes quiescent endothelium through an internal autocrine loop mechanism. J Cell Sci. 2005;118:771–780
  8. Roviezzo F, Tsigkos S, Kotanidou A, et al. Angiopoietin-2 causes inflammation in vivo by promoting vascular leakage. J Pharmacol Exp Ther. 2005;314:738–744
  9. Benest AV, Salmon AH, Wang W, et al. VEGF and angiopoietin-1 stimulate different angiogenic phenotypes that combine to enhance functional neovascularization in adult tissue. Microcirculation. 2006;13:423–437
  10. Zhang L, Yang N, Park JW, et al. Tumor-derived vascular endothelial growth factor up-regulates angiopoietin-2 in host endothelium and destabilizes host vasculature, supporting angiogenesis in ovarian cancer. Cancer Res. 2003;63:3403–3412
  11. Sato Y. Update on endogenous inhibitors of angiogenesis. Endothelium. 2006;13:147–155
  12. Sudhakar A, Nyberg P, Keshamouni VG, et al. Human alpha1 type IV collagen NC1 domain exhibits distinct antiangiogenic activity mediated by alpha1beta1 integrin. J Clin Invest. 2005;115:2801–2810
  13. Zent R, Pozzi A. Extracellular matrix and the development of disease: the role of its component in cancer progression. Adv Dev Biol. 2005;15:203–228
  14. Volpert OV, Zaichuk T, Zhou W, et al. Inducer-stimulated Fas targets activated endothelium for destruction by anti-angiogenic thrombospondin-1 and pigment epithelium-derived factor. Nat Med. 2002;8:349–357
  15. Steele FR, Chader GJ, Johnson LV, et al. Pigment epithelium-derived factor: neurotrophic activity and identification as a member of the serine protease inhibitor gene family. Proc Natl Acad Sci U S A. 1993;90:1526–1530
  16. Dawson DW, Volpert OV, Gillis P, et al. Pigment epithelium-derived factor: a potent inhibitor of angiogenesis. Science. 1999;285:245–248
  17. Zhang SX, Wang JJ, Gao G, et al. Pigment epithelium-derived factor downregulates vascular endothelial growth factor (VEGF) expression and inhibits VEGF-VEGF receptor 2 binding in diabetic retinopathy. J Mol Endocrinol. 2006;37:1–12
  18. Schrijvers BF, De Vriese AS, Flyvbjerg A. From hyperglycemia to diabetic kidney disease: the role of metabolic, hemodynamic, intracellular factors and growth factors/cytokines. Endocr Rev. 2004;25:971–1010
  19. van Dijk C, Berl T. Pathogenesis of diabetic nephropathy. Rev Endocr Metab Disord. 2004;5:237–248
  20. Zent R, Yan X, Su Y, et al. Glomerular injury is exacerbated in diabetic integrin alpha1-null mice. Kidney Int. 2006;70:460–470
  21. Susztak K, Raff AC, Schiffer M, et al. Glucose-induced reactive oxygen species cause apoptosis of podocytes and podocyte depletion at the onset of diabetic nephropathy. Diabetes. 2006;55:225–233
  22. Iglesias-De La Cruz MC, Ruiz-Torres P, Alcami J, et al. Hydrogen peroxide increases extracellular matrix mRNA through TGF-beta in human mesangial cells. Kidney Int. 2001;59:87–95
  23. Park SK, Kim J, Seomun Y, et al. Hydrogen peroxide is a novel inducer of connective tissue growth factor. Biochem Biophys Res Commun. 2001;284:966–971
  24. Forbes JM, Cooper ME, Oldfield MD, et al. Role of advanced glycation end products in diabetic nephropathy. J Am Soc Nephrol. 2003;14:S254–S258
  25. Nagase M, Shibata S, Yoshida S, et al. Podocyte injury underlies the glomerulopathy of Dahl salt-hypertensive rats and is reversed by aldosterone blocker. Hypertension. 2006;47:1084–1093
  26. Osterby R, Asplund J, Bangstad HJ, et al. Neovascularization at the vascular pole region in diabetic glomerulopathy. Nephrol Dial Transplant. 1999;14:348–352
  27. Nyengaard JR, Rasch R. The impact of experimental diabetes mellitus in rats on glomerular capillary number and sizes. Diabetologia. 1993;36:189–194
  28. Guo M, Ricardo SD, Deane JA, et al. A stereological study of the renal glomerular vasculature in the db/db mouse model of diabetic nephropathy. J Anat. 2005;207:813–821
  29. Kanesaki Y, Suzuki D, Uehara G, et al. Vascular endothelial growth factor gene expression is correlated with glomerular neovascularization in human diabetic nephropathy. Am J Kidney Dis. 2005;45:288–294
  30. Wang JJ, Zhang SX, Lu K, et al. Decreased expression of pigment epithelium-derived factor is involved in the pathogenesis of diabetic nephropathy. Diabetes. 2005;54:243–250
  31. Kim NH, Oh JH, Seo JA, et al. Vascular endothelial growth factor (VEGF) and soluble VEGF receptor FLT-1 in diabetic nephropathy. Kidney Int. 2005;67:167–177
  32. Iglesias-de la Cruz MC, Ziyadeh FN, Isono M, et al. Effects of high glucose and TGF-beta1 on the expression of collagen IV and vascular endothelial growth factor in mouse podocytes. Kidney Int. 2002;62:901–913
  33. Hohenstein B, Hausknecht B, Boehmer K, et al. Local VEGF activity but not VEGF expression is tightly regulated during diabetic nephropathy in man. Kidney Int. 2006;69:1654–1661
  34. Bortoloso E, Del Prete D, Dalla Vestra M, et al. Quantitative and qualitative changes in vascular endothelial growth factor gene expression in glomeruli of patients with type 2 diabetes. Eur J Endocrinol. 2004;150:799–807
  35. Eremina V, Quaggin SE. The role of VEGF-A in glomerular development and function. Curr Opin Nephrol Hypertens. 2004;13:9–15
  36. Eremina V, Sood M, Haigh J, et al. Glomerular-specific alterations of VEGF-A expression lead to distinct congenital and acquired renal diseases. J Clin Invest. 2003;111:707–716
  37. Uchida K, Uchida S, Nitta K, et al. Glomerular endothelial cells in culture express and secrete vascular endothelial growth factor. Am J Physiol. 1994;266:F81–F88
  38. Lee KS, Kim SR, Park SJ, et al. Hydrogen peroxide induces vascular permeability via regulation of vascular endothelial growth factor. Am J Respir Cell Mol Biol. 2006;35:190–197
  39. Yamagishi S, Inagaki Y, Okamoto T, et al. Advanced glycation end product-induced apoptosis and overexpression of vascular endothelial growth factor and monocyte chemoattractant protein-1 in human-cultured mesangial cells. J Biol Chem. 2002;277:20309–20315
  40. Woolf AS, Yuan HT. Angiopoietin growth factors and Tie receptor tyrosine kinases in renal vascular development. Pediatr Nephrol. 2001;16:177–184
  41. Satchell SC, Harper SJ, Tooke JE, et al. Human podocytes express angiopoietin 1, a potential regulator of glomerular vascular endothelial growth factor. J Am Soc Nephrol. 2002;13:544–550
  42. Satchell SC, Anderson KL, Mathieson PW. Angiopoietin 1 and vascular endothelial growth factor modulate human glomerular endothelial cell barrier properties. J Am Soc Nephrol. 2004;15:566–574
  43. Yamamoto Y, Maeshima Y, Kitayama H, et al. Tumstatin peptide, an inhibitor of angiogenesis, prevents glomerular hypertrophy in the early stage of diabetic nephropathy. Diabetes. 2004;53:1831–1840
  44. Ichinose K, Maeshima Y, Yamamoto Y, et al. Antiangiogenic endostatin peptide ameliorates renal alterations in the early stage of a type 1 diabetic nephropathy model. Diabetes. 2005;54:2891–2903
  45. Singh AK, Gudehithlu KP, Pegoraro AA, et al. Vascular factors altered in glucose-treated mesangial cells and diabetic glomeruli (Changes in vascular factors impair endothelial cell growth and matrix). Lab Invest. 2004;84:597–606
  46. Spranger J, Osterhoff M, Reimann M, et al. Loss of the antiangiogenic pigment epithelium-derived factor in patients with angiogenic eye disease. Diabetes. 2001;50:2641–2645
  47. Yamagishi S, Matsui T, Inoue H. Inhibition by advanced glycation end products (AGEs) of pigment epithelium-derived factor (PEDF) gene expression in microvascular endothelial cells. Drugs Exp Clin Res. 2005;31:227–232
  48. Wang JJ, Zhang SX, Mott R, et al. Salutary effect of pigment epithelium-derived factor in diabetic nephropathy: evidence for antifibrogenic activities. Diabetes. 2006;55:1678–1685
  49. Kang YS, Park YG, Kim BK, et al. Angiotensin II stimulates the synthesis of vascular endothelial growth factor through the p38 mitogen activated protein kinase pathway in cultured mouse podocytes. J Mol Endocrinol. 2006;36:377–388
  50. Uemura H, Nakaigawa N, Ishiguro H, et al. Antiproliferative efficacy of angiotensin II receptor blockers in prostate cancer. Curr Cancer Drug Targets. 2005;5:307–323
  51. Yoshiji H, Noguchi R, Kuriyama S, et al. Suppression of renin-angiotensin system attenuates hepatocarcinogenesis via angiogenesis inhibition in rats. Anticancer Res. 2005;25:3335–3340
  52. Yoshiji H, Kuriyama S, Noguchi R, et al. Angiotensin-I converting enzyme inhibitors as potential anti-angiogenic agents for cancer therapy. Curr Cancer Drug Targets. 2004;4:555–567
  53. Yoshiji H, Kuriyama S, Kawata M, et al. The angiotensin-I-converting enzyme inhibitor perindopril suppresses tumor growth and angiogenesis: possible role of the vascular endothelial growth factor. Clin Cancer Res. 2001;7:1073–1078
  54. Duh E, Aiello LP. Vascular endothelial growth factor and diabetes: the agonist versus antagonist paradox. Diabetes. 1999;48:1899–1906
  55. Aiello LP, Wong JS. Role of vascular endothelial growth factor in diabetic vascular complications. Kidney Int Suppl. 2000;77:S113–S119
  56. Satchell SC, Mathieson PW. Angiopoietins: microvascular modulators with potential roles in glomerular pathophysiology. J Nephrol. 2003;16:168–178
  57. de Vriese AS, Tilton RG, Elger M, et al. Antibodies against vascular endothelial growth factor improve early renal dysfunction in experimental diabetes. J Am Soc Nephrol. 2001;12:993–1000
  58. Flyvbjerg A, Dagnaes-Hansen F, De Vriese AS, et al. Amelioration of long-term renal changes in obese type 2 diabetic mice by a neutralizing vascular endothelial growth factor antibody. Diabetes. 2002;51:3090–3094
  59. Schrijvers BF, Flyvbjerg A, Tilton RG, et al. A neutralizing VEGF antibody prevents glomerular hypertrophy in a model of obese type 2 diabetes, the Zucker diabetic fatty rat. Nephrol Dial Transplant. 2006;21:324–329
  60. Schrijvers BF, De Vriese AS, Tilton RG, et al. Inhibition of vascular endothelial growth factor (VEGF) does not affect early renal changes in a rat model of lean type 2 diabetes. Horm Metab Res. 2005;37:21–25
  61. Gupta K, Zhang J. Angiogenesis: a curse or cure?. Postgrad Med J. 2005;81:236–242
  62. Zhang SX, Wang JJ, Lu K, et al. Therapeutic potential of angiostatin in diabetic nephropathy. J Am Soc Nephrol. 2006;17:475–486
  63. Griscelli F, Li H, Bennaceur-Griscelli A, et al. Angiostatin gene transfer: inhibition of tumor growth in vivo by blockage of endothelial cell proliferation associated with a mitosis arrest. Proc Natl Acad Sci U S A. 1998;95:6367–6372
  64. Sima J, Zhang SX, Shao C, et al. The effect of angiostatin on vascular leakage and VEGF expression in rat retina. FEBS Lett. 2004;564:19–23
  65. Chung AW, Hsiang YN, Matzke LA, et al. Reduced expression of vascular endothelial growth factor paralleled with the increased angiostatin expression resulting from the upregulated activities of matrix metalloproteinase-2 and -9 in human type 2 diabetic arterial vasculature. Circ Res. 2006;99:140–148
  66. Chen S, Lee JS, Iglesias-de la Cruz MC, et al. Angiotensin II stimulates alpha3(IV) collagen production in mouse podocytes via TGF-beta and VEGF signalling: implications for diabetic glomerulopathy. Nephrol Dial Transplant. 2005;20:1320–1328
  67. Goldin A, Beckman JA, Schmidt AM, et al. Advanced glycation end products: sparking the development of diabetic vascular injury. Circulation. 2006;114:597–605
  68. Wautier MP, Chappey O, Corda S, et al. Activation of NADPH oxidase by AGE links oxidant stress to altered gene expression via RAGE. Am J Physiol. 2001;280:E685–E694
  69. Pala L, Cresci B, Manuelli C, et al. Vascular endothelial growth factor receptor-2 and low affinity VEGF binding sites on human glomerular endothelial cells: biological effects and advanced glycosylation end products modulation. Microvasc Res. 2005;70:179–188
  70. Yamagishi S, Yonekura H, Yamamoto Y, et al. Advanced glycation end products-driven angiogenesis in vitro (Induction of the growth and tube formation of human microvascular endothelial cells through autocrine vascular endothelial growth factor). J Biol Chem. 1997;272:8723–8730
  71. Flyvbjerg A, Denner L, Schrijvers BF, et al. Long-term renal effects of a neutralizing RAGE antibody in obese type 2 diabetic mice. Diabetes. 2004;53:166–172
  72. Jensen LJ, Denner L, Schrijvers BF, et al. Renal effects of a neutralising RAGE-antibody in long-term streptozotocin-diabetic mice. J Endocrinol. 2006;188:493–501
  73. Kelly DJ, Gilbert RE, Cox AJ, et al. Aminoguanidine ameliorates overexpression of prosclerotic growth factors and collagen deposition in experimental diabetic nephropathy. J Am Soc Nephrol. 2001;12:2098–2107
  74. Booth AA, Khalifah RG, Todd P, et al. In vitro kinetic studies of formation of antigenic advanced glycation end products (AGEs) (Novel inhibition of post-Amadori glycation pathways). J Biol Chem. 1997;272:5430–5437
  75. Degenhardt TP, Alderson NL, Arrington DD, et al. Pyridoxamine inhibits early renal disease and dyslipidemia in the streptozotocin-diabetic rat. Kidney Int. 2002;61:939–950
  76. Zheng F, Zeng YJ, Plati AR, et al. Combined AGE inhibition and ACEi decreases the progression of established diabetic nephropathy in B6 db/db mice. Kidney Int. 2006;70:507–514
  77. Pozzi A, Moberg PE, Miles LA, et al. Elevated matrix metalloprotease and angiostatin levels in integrin alpha 1 knockout mice cause reduced tumor vascularization. Proc Natl Acad Sci U S A. 2000;97:2202–2207

 Supported in part by National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) grants R01-DK074359 (A.P.); RO1-DK 69921 (R.Z.), National Institutes of Health/NIDDK O’Brien Center grant P50-DK39261-16 (A.P., R.Z.), and a Merit award from the Department of Veterans Affairs (R.Z.).

PII: S0270-9295(07)00008-3

doi: 10.1016/j.semnephrol.2007.01.007

Seminars in Nephrology
Volume 27, Issue 2 , Pages 161-171 , March 2007