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Endothelial Growth Factor Receptors in Angiogenesis

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Biochemical Basis and Therapeutic Implications of Angiogenesis

Part of the book series: Advances in Biochemistry in Health and Disease ((ABHD,volume 6))

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Abstract

It is hard to underestimate the role of endothelial growth factor receptors in the generation of new blood vessels. This axis is involved in vascular development in embryos and angiogenesis in adults. As the signaling of these tyrosine kinase receptors has been elucidated, we have gained an appreciation of the complex interactions with other receptors, co-receptors, and downstream pathways.

Its involvement in pathology makes it a particularly tempting therapeutic target with its manipulation offering several theoretical benefits. The most intensely studied is the role of anti-VEGFR drugs in cancer chemotherapy. Initial trials were disappointing but a decade ago the first drug targeting the vascular endothelial growth factor (VEGF) axis was approved, providing a vital proof of concept. Therapies specifically targeting the receptor are in early development for prevention of neovascular diseases of the eye. Conversely, promotion of revascularization following vascular occlusion is another possible application being studied.

While these therapies show promise, the manipulation of VEGF receptors themselves remains a relatively small niche in the therapeutic armory. A deeper understanding of the receptor, its co-receptors, and the downstream web of signaling is required to complete the pieces of the puzzle and unlock the potential of this receptor pathway.

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References

  1. Gale NW, Yancopoulos GD (1999) Growth factors acting via endothelial cell-specific receptor tyrosine kinases: VEGFs, angiopoietins, and ephrins in vascular development. Genes Dev 13:1055–1066

    Article  CAS  PubMed  Google Scholar 

  2. Avraamides CJ, Garmy-Susini B, Varner JA (2008) Integrins in angiogenesis and lymphangiogenesis. Nat Rev Cancer 8:604–617

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Cross MJ, Claesson-Welsh L (2001) FGF and VEGF function in angiogenesis: signalling pathways, biological responses and therapeutic inhibition. Trends Pharmacol Sci 22:201–207

    Article  CAS  PubMed  Google Scholar 

  4. Sallinen H, Anttila M, Grohn O et al (2011) Cotargeting of VEGFR-1 and -3 and angiopoietin receptor Tie2 reduces the growth of solid human ovarian cancer in mice. Cancer Gene Ther 18:100–109

    Article  CAS  PubMed  Google Scholar 

  5. Bergers G, Hanahan D (2008) Modes of resistance to anti-angiogenic therapy. Nat Rev Cancer 8:592–603

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Azam F, Mehta S, Harris AL (2010) Mechanisms of resistance to antiangiogenesis therapy. Eur J Cancer 46:1323–1332

    Article  CAS  PubMed  Google Scholar 

  7. Augustin HG, Young Koh G, Thurston G, Alitalo K (2009) Control of vascular morphogenesis and homeostasis through the angiopoietin-tie system. Nat Rev Mol Cell Biol 10:165–177

    Article  CAS  PubMed  Google Scholar 

  8. Senger DR, Connolly DT, Van De Water L et al (1990) Purification and NH2-terminal amino acid sequence of guinea pig tumor-secreted vascular permeability factor. Cancer Res 50:1774–1778

    CAS  PubMed  Google Scholar 

  9. Olsson A-K, Dimberg A, Kreuger J, Claesson-Welsh L (2006) VEGF receptor signalling—in control of vascular function. Nat Rev Mol Cell Biol 7:359–371

    Article  CAS  PubMed  Google Scholar 

  10. Hicklin DJ, Ellis LM (2005) Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis. J Clin Oncol 23:1011–1027

    Article  CAS  PubMed  Google Scholar 

  11. Ivy SP, Wick JY, Kaufman BM (2009) An overview of small-molecule inhibitors of VEGFR signaling. Nat Rev Clin Oncol 6:569–579

    Article  CAS  PubMed  Google Scholar 

  12. Kearney JB, Kappas NC, Ellerstrom C et al (2004) The VEGF receptor flt-1 (VEGFR-1) is a positive modulator of vascular sprout formation and branching morphogenesis. Blood 103:4527–4535

    Article  CAS  PubMed  Google Scholar 

  13. Muller YA, Christinger HW, Keyt BA, de Vos AM (1997) The crystal structure of vascular endothelial growth factor (VEGF) refined to 1.93 Å resolution: multiple copy flexibility and receptor binding. Structure 5:1325–1338

    Article  CAS  PubMed  Google Scholar 

  14. Ng Y-S, Krilleke D, Shima DT (2006) VEGF function in vascular pathogenesis. Exp Cell Res 312:527–537

    Article  CAS  PubMed  Google Scholar 

  15. Robinson C, Stringer S (2001) The splice variants of vascular endothelial growth factor (VEGF) and their receptors. J Cell Sci 114:853–865

    CAS  PubMed  Google Scholar 

  16. Bruce D, Tan PH (2011) Vascular endothelial growth factor receptors and the therapeutic targeting of angiogenesis in cancer: where do we go from here? Cell Commun Adhes 18:85–103

    CAS  PubMed  Google Scholar 

  17. Houck KA, Leung DW, Rowland AM et al (1992) Dual regulation of vascular endothelial growth factor bioavailability by genetic and proteolytic mechanisms. J Biol Chem 267:26031–26037

    CAS  PubMed  Google Scholar 

  18. Park J, Keller G, Ferrara N (1993) The vascular endothelial growth factor (VEGF) isoforms: differential deposition into the subepithelial extracellular matrix and bioactivity of extracellular matrix-bound VEGF. Mol Biol Cell 4:1317–1326

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Ruhrberg C, Gerhardt H, Golding M et al (2002) Spatially restricted patterning cues provided by heparin-binding VEGF-A control blood vessel branching morphogenesis. Genes Dev 16:2684–2698

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Keyt BA, Berleau LT, Nguyen HV et al (1996) The carboxyl-terminal domain (111165) of vascular endothelial growth factor is critical for its mitogenic potency. J Biol Chem 271:7788–7795

    Article  CAS  PubMed  Google Scholar 

  21. Schwartz JD, Rowinsky EK, Youssoufian H et al (2010) Vascular endothelial growth factor receptor-1 in human cancer. Cancer 116(S4):1027–1032

    Article  CAS  PubMed  Google Scholar 

  22. Joukov V, Pajusola K, Kaipainen A, Chilov D et al (1996) A novel vascular endothelial growth factor, VEGF-C, is a ligand for the Flt4 (VEGFR-3) and KDR (VEGFR-2) receptor tyrosine kinases. EMBO J 15:9

    Google Scholar 

  23. Kaipainen A, Korhonen J, Pajusola K et al (1993) The related FLT4, FLT1, and KDR receptor tyrosine kinases show distinct expression patterns in human fetal endothelial cells. J Exp Med 178:2077–2088

    Article  CAS  PubMed  Google Scholar 

  24. Rahimi N, Golde TE, Meyer RD (2009) Identification of ligand-induced proteolytic cleavage and ectodomain shedding of VEGFR-1/FLT1 in leukemic cancer cells. Cancer Res 69:2607–2614

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Park JE, Chen HH, Winer J et al (1994) Placenta growth factor. Potentiation of vascular endothelial growth factor bioactivity, in vitro and in vivo, and high affinity binding to Flt-1 but not to Flk-1/KDR. J Biol Chem 269:25646–25654

    CAS  PubMed  Google Scholar 

  26. Kappas NC, Zeng G, Chappell JC et al (2008) The VEGF receptor Flt-1 spatially modulates Flk-1 signaling and blood vessel branching. J Cell Biol 181:847–858

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Huang K, Andersson C, Roomans GM et al (2001) Signaling properties of VEGF receptor-1 and -2 homo- and heterodimers. Int J Biochem Cell Biol 33:315–324

    Article  CAS  PubMed  Google Scholar 

  28. Dougher M, Terman BI (1999) Autophosphorylation of KDR in the kinase domain is required for maximal VEGF-stimulated kinase activity and receptor internalization. Oncogene 18:29

    Article  Google Scholar 

  29. Takahashi T, Yamaguchi S, Chida K, Shibuya M (2001) A. Single autophosphorylation site on KDR/Flk-1 is essential for VEGF-A-dependent activation of PLC-[gamma] and DNA synthesis in vascular endothelial cells. EMBO J 20:2768–2778

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Holmqvist K, Cross MJ, Rolny C et al (2004) The adaptor protein shb binds to tyrosine 1175 in vascular endothelial growth factor (VEGF) receptor-2 and regulates VEGF-dependent cellular migration. J Biol Chem 279:22267–22275

    Article  CAS  PubMed  Google Scholar 

  31. Le Boeuf F, Houle F, Huot J (2004) Regulation of vascular endothelial growth factor receptor 2-mediated phosphorylation of focal adhesion kinase by heat shock protein 90 and Src kinase activities. J Biol Chem 279:39175–39185

    Article  PubMed  Google Scholar 

  32. Meadows KN, Bryant P, Pumiglia K (2001) Vascular endothelial growth factor induction of the angiogenic phenotype requires Ras activation. J Biol Chem 276:49289–49298

    Article  CAS  PubMed  Google Scholar 

  33. McMullen ME, Bryant PW, Glembotski CC et al (2005) Activation of p38 has opposing effects on the proliferation and migration of endothelial cells. J Biol Chem 280:20995–21003

    Article  CAS  PubMed  Google Scholar 

  34. Yamaoka-Tojo M, Ushio-Fukai M, Hilenski L et al (2004) IQGAP1, a novel vascular endothelial growth factor receptor binding protein, is involved in reactive oxygen species-dependent endothelial migration and proliferation. Circ Res 95:276–283

    Article  CAS  PubMed  Google Scholar 

  35. Kaipainen A, Korhonen J, Mustonen T et al (1995) Expression of the fms-like tyrosine kinase 4 gene becomes restricted to lymphatic endothelium during development. Proc Natl Acad Sci U S A 92:3566–3570

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Cross MJ, Dixelius J, Matsumoto T, Claesson-Welsh L (2003) VEGF-receptor signal transduction. Trends Biochem Sci 28:488–494

    Article  CAS  PubMed  Google Scholar 

  37. Dixelius J, Mäkinen T, Wirzenius M et al (2003) Ligand-induced vascular endothelial growth factor receptor-3 (VEGFR-3) heterodimerization with VEGFR-2 in primary lymphatic endothelial cells regulates tyrosine phosphorylation sites. J Biol Chem 278:40973–40979

    Article  CAS  PubMed  Google Scholar 

  38. Makinen T, Veikkola T, Mustjoki S et al (2001) Isolated lymphatic endothelial cells transduce growth, survival and migratory signals via the VEGF-C/D receptor VEGFR-3. EMBO J 20:4762–4773

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Hamada K, Oike Y, Takakura N et al (2000) VEGF-C signaling pathways through VEGFR-2 and VEGFR-3 in vasculoangiogenesis and hematopoiesis. Blood 96:3793–3800

    CAS  PubMed  Google Scholar 

  40. Matsumura K, Hirashima M, Ogawa M et al (2003) Modulation of VEGFR-2-mediated endothelial- cell activity by VEGF-C/VEGFR-3. Blood 101:1367–1374

    Article  CAS  PubMed  Google Scholar 

  41. Tammela T, Zarkada G, Nurmi H et al (2011) VEGFR-3 controls tip to stalk conversion at vessel fusion sites by reinforcing notch signalling. Nat Cell Biol 13:1202–1213

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Zachary I, Morgan RD (2011) Therapeutic angiogenesis for cardiovascular disease: biological context, challenges, prospects. Heart 97:181–189

    Article  CAS  PubMed  Google Scholar 

  43. Staton C, Yang Z, Reed M, Brown N (2008) Bevacizumab resistance in breast cancer: are neuropilins the key? Breast Cancer Res 10(suppl 2):P75

    Article  PubMed Central  Google Scholar 

  44. Xu D, Fuster MM, Lawrence R, Esko JD (2011) Heparan sulfate regulates VEGF165 and VEGF121-mediated vascular hyperpermeability. J Biol Chem 1:9

    Google Scholar 

  45. Le Jan S, Hayashi M, Kasza Z et al (2012) Functional overlap between chondroitin and heparan sulfate proteoglycans during VEGF-induced sprouting angiogenesis. Arterioscler Thromb Vasc Biol 32:1255–1263

    Article  PubMed  PubMed Central  Google Scholar 

  46. Smith NR, Baker D, James NH et al (2010) Vascular endothelial growth factor receptors VEGFR-2 and VEGFR-3 are localized primarily to the vasculature in human primary solid cancers. Clin Cancer Res 16:3548–3561

    Article  CAS  PubMed  Google Scholar 

  47. Yang AD, Camp ER, Fan F et al (2006) Vascular endothelial growth factor receptor-1 activation mediates epithelial to mesenchymal transition in human pancreatic carcinoma cells. Cancer Res 66:46–51

    Article  CAS  PubMed  Google Scholar 

  48. André T, Kotelevets L, Vaillant J-C et al (2000) Vegf, vegf-B, vegf-C and their receptors KDR, FLT-1 and FLT-4 during the neoplastic progression of human colonic mucosa. Int J Cancer 86:174–181

    Article  PubMed  Google Scholar 

  49. Vincent L, Jin DK, Karajannis MA et al (2005) Fetal stromal–dependent paracrine and intracrine vascular endothelial growth factor-a/vascular endothelial growth factor receptor-1 signaling promotes proliferation and motility of human primary myeloma cells. Cancer Res 65:3185–3192

    Article  CAS  PubMed  Google Scholar 

  50. Graepler F, Verbeek B, Graeter T et al (2005) Combined endostatin/sFlt-1 antiangiogenic gene therapy is highly effective in a rat model of HCC. Hepatology 41:879–886

    Article  CAS  PubMed  Google Scholar 

  51. Youssoufian H, Hicklin DJ, Rowinsky EK (2007) Review: monoclonal antibodies to the vascular endothelial growth factor receptor-2 in cancer therapy. Clin Cancer Res 13:5544s–5548s

    Article  CAS  PubMed  Google Scholar 

  52. Prewett M, Huber J, Li Y et al (1999) Antivascular endothelial growth factor receptor (fetal liver kinase 1) monoclonal antibody inhibits tumor angiogenesis and growth of several mouse and human tumors. Cancer Res 59:5209–5218

    CAS  PubMed  Google Scholar 

  53. Lyden D, Hattori K, Dias S et al (2001) Impaired recruitment of bone-marrow–derived endothelial and hematopoietic precursor cells blocks tumor angiogenesis and growth. Nat Med 7:8

    Article  Google Scholar 

  54. Su J-L, Yang P-C, Shih J-Y et al (2006) The VEGF-C/Flt-4 axis promotes invasion and metastasis of cancer cells. Cancer Cell 9:209–223

    Article  CAS  PubMed  Google Scholar 

  55. Hoshida T, Isaka N, Hagendoorn J et al (2006) Imaging steps of lymphatic metastasis reveals that vascular endothelial growth factor-C increases metastasis by increasing delivery of cancer cells to lymph nodes: therapeutic implications. Cancer Res 66:8065–8075

    Article  CAS  PubMed  Google Scholar 

  56. Ghanem MA, van Steenbrugge GJ, Sudaryo MK et al (2003) Expression and prognostic relevance of vascular endothelial growth factor (VEGF) and its receptor (FLT-1) in nephroblastoma. J Clin Pathol 56:107–113

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Plate KH, Breier G, Weich HA et al (1994) Vascular endothelial growth factor and glioma angiogenesis: coordinate induction of VEGF receptors, distribution of VEGF protein and possible in vivo regulatory mechanisms. Int J Cancer 59:520–529

    Article  CAS  PubMed  Google Scholar 

  58. Seto T, Higashiyama M, Funai H et al (2006) Prognostic value of expression of vascular endothelial growth factor and its flt-1 and KDR receptors in stage I non-small-cell lung cancer. Lung Cancer 53:91–96

    Article  PubMed  Google Scholar 

  59. Kaplan RN, Rafii S, Lyden D (2006) Preparing the “soil”: the premetastatic niche. Cancer Res 66:11089–11093

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Hiratsuka S, Nakamura K, Iwai S et al (2002) MMP9 induction by vascular endothelial growth factor receptor-1 is involved in lung-specific metastasis. Cancer 2:289–300

    CAS  Google Scholar 

  61. Dawson MR, Duda DG, Fukumura D, Jain RK (2009) VEGFR1-activity-independent metastasis formation. Nature 461:E4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Mimori K, Fukagawa T, Kosaka Y et al (2008) Hematogenous metastasis in gastric cancer requires isolated tumor cells and expression of vascular endothelial growth factor receptor-1. Clin Cancer Res 14:2609–2616

    Article  CAS  PubMed  Google Scholar 

  63. Bellamy WT, Richter L, Sirjani D et al (2001) Vascular endothelial cell growth factor is an autocrine promoter of abnormal localized immature myeloid precursors and leukemia progenitor formation in myelodysplastic syndromes. Blood 97:1427–1434

    Article  CAS  PubMed  Google Scholar 

  64. Price DJ, Miralem T, Jiang S et al (2001) Role of vascular endothelial growth factor in the stimulation of cellular invasion and signaling of breast cancer cells. Cell Growth Differ 12:129–135

    CAS  PubMed  Google Scholar 

  65. Hamerlik P, Lathia JD, Rasmussen R et al (2012) Autocrine VEGF–VEGFR2–neuropilin-1 signaling promotes glioma stem-like cell viability and tumor growth. J Exp Med 209:507–520

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Boehm T, Folkman J, Browder T, O’Reilly MS (1997) Antiangiogenic therapy of experimental cancer does not induce acquired drug resistance. Nature 390:404–407

    Article  CAS  PubMed  Google Scholar 

  67. Roberts N, Kloos B, Cassella M et al (2006) Inhibition of VEGFR-3 activation with the antagonistic antibody more potently suppresses lymph node and distant metastases than inactivation of VEGFR-2. Cancer Res 66:2650–2657

    Article  CAS  PubMed  Google Scholar 

  68. Bradley DP, Tessier JJ, Lacey T et al (2009) Examining the acute effects of cediranib (RECENTIN, AZD2171) treatment in tumor models: a dynamic contrast-enhanced MRI study using gadopentate. Magn Reson Imaging 27:377–384

    Article  CAS  PubMed  Google Scholar 

  69. Winkler F, Kozin SV, Tong RT et al (2004) Kinetics of vascular normalization by VEGFR2 blockade governs brain tumor response to radiation: role of oxygenation, angiopoietin-1, and matrix metalloproteinases. Cancer Cell 6:553–563

    CAS  PubMed  Google Scholar 

  70. Bruce D, Tan PH (2011) Blocking the interaction of vascular endothelial growth factor receptors with their ligands and their effector signaling as a novel therapeutic target for cancer: time for a new look? Expert Opin Investig Drugs 20:1413–1434

    Article  CAS  PubMed  Google Scholar 

  71. Demetri GD, van Oosterom AT, Garrett CR et al (2006) Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: a randomised controlled trial. Lancet 368:1329–1338

    Article  CAS  PubMed  Google Scholar 

  72. Motzer RJ, Hutson TE, Tomczak P et al (2007) Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med 356:115–124

    Article  CAS  PubMed  Google Scholar 

  73. Potapova O, Laird AD, Nannini MA et al (2006) Contribution of individual targets to the antitumor efficacy of the multitargeted receptor tyrosine kinase inhibitor SU11248. Mol Cancer Ther 5:1280–1289

    Article  CAS  PubMed  Google Scholar 

  74. Connock M, Round J, Bayliss S et al (2010) Sorafenib for the treatment of advanced hepatocellular carcinoma. Health Technol Assess 14(suppl 1):17–21

    Article  PubMed  Google Scholar 

  75. Takahashi O, Komaki R, Smith PD et al (2012) Combined MEK and VEGFR inhibition in orthotopic human lung cancer models results in enhanced inhibition of tumor angiogenesis, growth, and metastasis. Clin Cancer Res 18:1641–1654

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Hurwitz H, Fehrenbacher L, Novotny W et al (2004) Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 350:2335–2342

    Article  CAS  PubMed  Google Scholar 

  77. Shaheen RM, Ahmad SA, Liu W et al (2001) Inhibited growth of colon cancer carcinomatosis by antibodies to vascular endothelial and epidermal growth factor receptors. Br J Cancer 85:584–589

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Wang F-Q, Barfield E, Dutta S et al (2009) VEGFR-2 silencing by small interference RNA (siRNA) suppresses LPA-induced epithelial ovarian cancer (EOC) invasion. Gynecol Oncol 115:414–423

    Article  CAS  PubMed  Google Scholar 

  79. Eskens FA, Verweij J (2006) The clinical toxicity profile of vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor (VEGFR) targeting angiogenesis inhibitors; a review. Eur J Cancer 42:3127–3139

    Article  CAS  PubMed  Google Scholar 

  80. Cheng H, Force T (2010) Molecular mechanisms of cardiovascular toxicity of targeted cancer therapeutics. Circ Res 106:21–34

    Article  CAS  PubMed  Google Scholar 

  81. Bhisitkul RB (2006) Vascular endothelial growth factor biology: clinical implications for ocular treatments. Br J Ophthalmol 90:1542–1547

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Asato R, Kita T, Kawahara S et al (2011) Vitreous levels of soluble vascular endothelial growth factor receptor (VEGFR)-1 in eyes with vitreoretinal diseases. Br J Ophthalmol 95:1745–1748

    Article  PubMed  Google Scholar 

  83. Montoro-García S, Lip P-L, Chan C-C, Lip GYH (2011) Soluble vascular endothelial growth factor receptor (VEGFR)-2 in macular oedema—a mechanism for regulating angiogenesis? Br J Ophthalmol 95:757–758

    Article  PubMed  Google Scholar 

  84. Usui T, Ishida S, Yamashiro K et al (2004) VEGF164(165) as the pathological isoform: differential leukocyte and endothelial responses through VEGFR1 and VEGFR2. Invest Ophthalmol Vis Sci 45:368–374

    Article  PubMed  Google Scholar 

  85. Pieramici DJ, Rabena MD (2008) Anti-VEGF therapy: comparison of current and future agents. Eye (Lond) 22:1330–1336

    Article  CAS  Google Scholar 

  86. Maier P, Unsoeld AS, Junker B et al (2005) Intravitreal injection of specific receptor tyrosine kinase inhibitor PTK787/ZK222 584 improves ischemia-induced retinopathy in mice. Graefes Arch Clin Exp Ophthalmol 243:593–600

    Article  CAS  PubMed  Google Scholar 

  87. Keskin U, Totan Y, Karadağ R et al (2012) Inhibitory effects of SU5416, a selective vascular endothelial growth factor receptor tyrosine kinase inhibitor, on experimental corneal neovascularization. Ophthalmic Res 47:13–18

    Article  CAS  PubMed  Google Scholar 

  88. Clinicaltrials.gov. A study of the safety and efficacy of AG-013958 in subjects with subfoveal choroidal neovascularization associated with age-related macular degeneration. Clinicaltrials.gov identifier: NCT00090532 http://clinicaltrials.gov/ct2/show/NCT00090532?term=ag+013958%26rank=12011

  89. Barakat MR, Kaiser P (2009) VEGF inhibitors for the treatment of neovascular age-related macular degeneration. Expert Opin Investig Drugs 18:637–646

    Article  CAS  PubMed  Google Scholar 

  90. Lee S, Chen TT, Barber CL et al (2007) Autocrine VEGF signaling is required for vascular homeostasis. Cell 130:691–703

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Du H, Li P, Pan Y et al (2010) Vascular endothelial growth factor signaling implicated in neuroprotective effects of placental growth factor in an in vitro ischemic model. Brain Res 1357:1–8

    Article  CAS  PubMed  Google Scholar 

  92. Wu H, Jiang H, Lu D et al (2011) Induction of angiogenesis and modulation of vascular endothelial growth factor receptor-2 by simvastatin after traumatic brain injury. Neurosurgery 68:1363–1371; discussion 1371

    Google Scholar 

  93. USNIH (2010) ClinicalTrials.gov. http://www.clinicaltrials.gov/ct2/home. Accessed 20 May 2011

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Authors and Affiliations

  1. Oxford University Hospitals NHS Trust, John Radcliffe Hospital, Oxford, OX3 9DU, UK

    David J. Bruce

  2. Department of Immunology, Division of Medicine, Imperial College London, Hammersmith Hospital, London, UK

    Peng H. Tan

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  1. David J. Bruce
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  2. Peng H. Tan
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Correspondence to David J. Bruce .

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Editors and Affiliations

  1. Divison of Cardiovascular Medicine, University of Arkansas for Medical Sciences, Central Arkansas Veterans Healthcare System, Little Rock, Arkansas, USA

    Jawahar L. Mehta

  2. Department of Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA

    Pankaj Mathur

  3. Institute of Cardiovascular Sciences, St. Boniface Hospital Albrechtsen Research Centre, Department of Physiology and Pathophysiology, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada

    Naranjan S. Dhalla

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Bruce, D.J., Tan, P.H. (2017). Endothelial Growth Factor Receptors in Angiogenesis. In: Mehta, J., Mathur, P., Dhalla, N. (eds) Biochemical Basis and Therapeutic Implications of Angiogenesis. Advances in Biochemistry in Health and Disease, vol 6. Springer, Cham. https://doi.org/10.1007/978-3-319-61115-0_1

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