The Biology of Vascular Endothelial Growth Factor, a Specific Regulator of Angiogenesis

  • Napoleone Ferrara
Part of the Serono Symposia USA Norwell, Massachusetts book series (SERONOSYMP)

Abstract

The establishment of a vascular supply is required for organ development and differentiation as well as for tissue repair and reproductive functions in the adult (1–3). Neovascularization (angiogenesis) is also implicated in the pathogenesis of a number of disorders: proliferative retinopathies, age-related macular degeneration, tumors, rheumatoid arthritis, and psoriasis. In the case of proliferative retinopathies and age-related macular degeneration, the new blood vessels are responsible for many of the destructive events characteristic of these conditions, as leakage and bleeding may ultimately lead to retinal detachment or irreversible damage to the macula (4). Conversely, in neoplasms neovascularization provides nourishment to the growing tumor, thus allowing tumor cells to express their critical growth advantage (2, 3). Accordingly, a strong correlation has been noted between density of microvessels in primary breast cancers and their nodal metastases and patient survival (5, 6). Similarly, a correlation has been reported between vascularity and invasive behavior in several other tumors (7–11).

Keywords

Permeability Ischemia Heparin Retina Oncol 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Folkman J, Shing Y. Angiogenesis. J Biol Chem 1992;267:10931–4.PubMedGoogle Scholar
  2. 2.
    Klagsbrun M, D’Amore PA. Regulators of angiogenesis. Annu Rev Physiol 1991;53:217–39.PubMedGoogle Scholar
  3. 3.
    Folkman J. What is the evidence that tumors are angiogenesis-dependent? J Natl Cancer Inst 1991;82:4–6.Google Scholar
  4. 4.
    Garner A. Vascular diseases. In: Garner A, Klintworth GK, eds. Pathobiology of ocular disease. A dynamic approach, 2nd ed. New York: Marcel Dekker, 1994:1625–710.Google Scholar
  5. 5.
    Weidner N, Semple P, Welch W, Folkman J. Tumor angiogenesis and metastasis. Correlation in invasive breast carcinoma. N Engl J Med 1991; 324:1–6.PubMedGoogle Scholar
  6. 6.
    Weidner N, Folkman J, Pozza F, et al. Tumor angiogenesis: a new significant and independent prognostic indicator in early-stage breast carcinoma. J Natl Cancer Inst 1992;84:1875–88.PubMedGoogle Scholar
  7. 7.
    Wakui S, Furusato M, Sasaki H, et al. Tumor angiogenesis in prostatic carcinoma with and without bone metastasis: a morphometric study. J Pathol 1992;168:257–62.PubMedGoogle Scholar
  8. 8.
    Chodak GW, Haudenschild C, Gittes RF, Folkman J. Angiogenic activity as a marker of neoplastic and preneoplastic lesions of the human bladder. Ann Surg 1980;192:762–71.PubMedGoogle Scholar
  9. 9.
    Macchiarini P, Fontanini G, Hardin MJ, Squartini F, Angeletti CA. Relation of neovascularization to metastasis of non-small cell lung carcinoma. Lancet 1992;340:145–6.PubMedGoogle Scholar
  10. 10.
    Sillman F, Boyce J, Fruchter R. The significance of atypical vessels and neovascularization in cervical neoplasias. Am J Obstet Gynecol 1981; 139:154–7.PubMedGoogle Scholar
  11. 11.
    Smith-McCune KS, Weidner N. Demonstration and characterization of the angiogenic properties of cervical dysplasia. Cancer Res 1994;54:804–8.Google Scholar
  12. 12.
    Ferrara N, Henzel WJ. Pituitary follicular cells secrete a novel heparin-binding growth factor specific for vascular endothelial cells. Biochem Biophys Res Commun 1989;161:851–9.PubMedGoogle Scholar
  13. 13.
    Ferrara N, Houck K, Jakeman L, Leung DW. Molecular and biological properties of the vascular endothelial growth factor family of proteins. Endocr Rev 1992;13:18–32.PubMedGoogle Scholar
  14. 14.
    Ploüet J, Schilling J, Gospodarowicz D. Isolation and characterization of a newly identified endothelial cell mitogen produced by AtT20 cells. EMBO J 1989;8:3801–7.PubMedGoogle Scholar
  15. 15.
    Conn G, Bayne M, Soderman L, et al. Amino acid and cDNA sequence of a vascular endothelial cell mitogen homologous to platelet-derived growth factor. Proc Nati Acad Sci USA 1990;87:2628–32.Google Scholar
  16. 16.
    Breier G, Albrecht U, Sterrer S, Risau W. Expression of vascular endothelial growth factor during embryonic angiogenesis and endothelial cell differentiation. Development 1992;114:521–32.PubMedGoogle Scholar
  17. 17.
    Phillips HS, Hains J, Leung DW, Ferrara N. Vascular endothelial growth factor is expressed in rat corpus luteum. Endocrinology 1990;127:965–68.PubMedGoogle Scholar
  18. 18.
    Shweiki D, Itin A, Neufeld G, Gitay-Goren H, Keshet E. Patterns of expression of vascular endothelial growth factor (VEGF) and VEGF receptors in mice suggest a role in hormonally regulated angiogenesis. J Clin Invest 1993;91:2235–43.PubMedGoogle Scholar
  19. 19.
    Banai S, Jaktlish MT, Shou M, et al. Angiogenic-induced enhancement of collateral blood flow to ischemic myocardium by vascular endothelial growth factor in dogs. Circulation 1994;89:2183–9.PubMedGoogle Scholar
  20. 20.
    Harada K, Friedman M, Lopez J, et al. Vascular endothelial growth factor improves coronary flow and myocardial function in chronically ischemic porcine hearts. Am J Physiol 1996;270:H1791–802.PubMedGoogle Scholar
  21. 21.
    Takeshita S, Zhung L, Brogi E, et al. Therapeutic angiogenesis: a single intra-arterial bolus of vascular endothelial growth factor augments collateral vessel formation in a rabbit ischemic hindlimb model. J Clin Invest 1994;93:662–70.PubMedGoogle Scholar
  22. 22.
    Takeshita S, Zheng LP, Cheng D, et al. Therapeutic angiogenesis following arterial gene transfer of vascular endothelial in a rabbit model of hindlimb ischemia. Biochem Biophys Res Commun 1996;227:628–35.PubMedGoogle Scholar
  23. 23.
    Kim KJ, Li B, Winer J, et al. Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumour growth in vivo. Nature 1993;362:841–4.PubMedGoogle Scholar
  24. 24.
    Aiello LP, Avery R, Arrigg R, et al. Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders. N Engl J Med 1994;331:1480–7.PubMedGoogle Scholar
  25. 25.
    Ferrara N. Vascular endothelial growth factor-the trigger for neovascularization in the eye. Lab Invest 1995;72:615–18.PubMedGoogle Scholar
  26. 26.
    Leung DW, Cachianes G, Kuang W-J, Goeddel DV, Ferrara N. Vascular endothelial growth factor is a secreted angiogenic mitogen. Science 1989; 246:1306–9.PubMedGoogle Scholar
  27. 27.
    Phillips GD, Stone AM, Jones BD, Schultz JC, Whitehead RA, Knighton DR. Vascular endothelial growth factor (rhVEGF165) stimulates direct angiogenesis in the rabbit cornea. In Vivo 1995;8:961–5.Google Scholar
  28. 28.
    Connolly DT, Heuvelman DM, Nelson R, et al. Tumor vascular permeability factor stimulates endothelial cell growth and angiogenesis. J Clin Invest 1989;84:1470–8.PubMedGoogle Scholar
  29. 29.
    Pepper MS, Ferrara N, Orci L, Montesano R. Potent synergism between vascular endothelial growth factor and basic fibroblast growth factor in the induction of angiogenesis in vitro. Biochem Biophys Res Commun 1992; 189:824–31.PubMedGoogle Scholar
  30. 30.
    Nicosia RF, Nicosia SV, Smith M. Vascular endothelial growth factor, platelet-derived growth factor and insulin-like growth factor-1 promote rat aortic angiogenesis in vitro. Am J Pathol 1995;145:1023–29.Google Scholar
  31. 31.
    Pepper MS, Ferrara N, Orci L, Montesano R. Vascular endothelial growth factor (VEGF) induces plasminogen activators and plasminogen activator inhibitor type 1 in microvascular endothelial cells. Biochem Biophys Res Commun 1991;181:902–8.PubMedGoogle Scholar
  32. 32.
    Unemori E, Ferrara N, Bauer EA, Amento EP. Vascular endothelial growth factor induces interstitial collagenase expression in human endothelial cells. J Cell Physiol 1992;153:557–62.PubMedGoogle Scholar
  33. 33.
    Mandriota S, Montesano R, Orci L, et al. Vascular endothelial growth factor increses urokinase receptor expression in vascular endothelial cells. J Biol Chem 1995;270:9709–16.PubMedGoogle Scholar
  34. 34.
    Connolly DT, Olander JV, Heuvelman D, et al. Human vascular permeability factor. Isolation from U937 cells. J Biol Chem 1989;254:20017–24.Google Scholar
  35. 35.
    Keck PJ, Hauser SD, Krivi G, et al. Vascular permeability factor, an endothelial cell mitogen related to platelet derived growth factor. Science 1989;246:1309–12.PubMedGoogle Scholar
  36. 36.
    Senger DR, Galli SJ, Dvorak AM, Perruzzi CA, Harvey VS, Dvorak HF. Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid. Science 1983;219:983–5.PubMedGoogle Scholar
  37. 37.
    Dvorak HF, Harvey VS, Estrella P, Brown LF, McDonagh J, Dvorak AM. Fibrin containing gels induce angiogenesis: implications for tumor stroma generation and wound healing. Lab Invest 1987;57:673–86.PubMedGoogle Scholar
  38. 38.
    Pekala P, Marlow M, Heuvelman D, Connolly D. Regulation of hexose transportin aortic endothelial cells by vascular permeability factor and tumor necrosis factor-alpha, but not by insulin. J Biol Chem 1990;265:18051–4.PubMedGoogle Scholar
  39. 39.
    Clauss M, Gerlach M, Gerlach H, et al. Vascular permeability factor: a tumor-derived polypeptide that induces endothelial cell and monocyte procoagulant activity, and promotes monocyte migration. J Exp Med 1990;172:1535–45.PubMedGoogle Scholar
  40. 40.
    Ku DD, Zaleski JK, Liu S, Brock T. Vascular endothelial growth factor induces EDRF-dependent relaxation of coronary arteries. Am J Physiol 1993;265:H586–92.PubMedGoogle Scholar
  41. 41.
    Park JE, Chen H, Winer J, Houck K, Ferrara N. 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 1994;269:25646–54.PubMedGoogle Scholar
  42. 42.
    Maglione D, Guerriero V, Viglietto G, Delli-Bovi P, Persico MG. Isolation of a human placenta cDNA coding for a protein related to the vascular permeability factor. Proc Natl Acad Sci USA 1991;88:9267–71.PubMedGoogle Scholar
  43. 43.
    Tisher E, Mitchell R, Hartmann T, et al. The human gene for vascular endothelial growth factor. J Biol Chem 1991;266:11947–54.Google Scholar
  44. 44.
    Houck KA, Ferrara N, Winer J, Cachianes G, Li B, Leung DW. The vascular endothelial growth factor family: identification of a fourth molecular species and characterization of alternative splicing of RNA. Mol Endocrinol 1991;5:1806–14.PubMedGoogle Scholar
  45. 45.
    Houck KA, Leung DW, Rowland AM, Winer J, Ferrara N. Dual regulation of vascular endothelial growth factor bioavailability by genetic and proteolytic mechanisms. J Biol Chem 1992;267:26031–7.PubMedGoogle Scholar
  46. 46.
    Park JE, Keller G-A, Ferrara N. The vascular endothelial growth factor (VEGF) isoforms: differential deposition into the subepithelial extracellular matrix and bioactivity of ECM-bound VEGF. Mol Biol Cell 1993;4:1317–26.PubMedGoogle Scholar
  47. 47.
    Mignatti P, Tsuboi R, Robbins E, Rifkin DB. In vitro angiogenesis on the human amniotic membrane: requirement for basic fibroblast growth factor-induced proteinases. J Cell Biol 1989;108:671–82.PubMedGoogle Scholar
  48. 48.
    DiSalvo J, Bayne ML, Conn G, et al. Purification and characterization of a naturally occurring vascular endothelial growth factor placenta growth factor heterodimer. J Biol Chem 1995;270:7717–23.PubMedGoogle Scholar
  49. 49.
    Minchenko A, Bauer T, Salceda S, Caro J. Hypoxic stimulation of vascular endothelial growth factor expression in vivo and in vitro. Lab Invest 1994;71:374–9.PubMedGoogle Scholar
  50. 50.
    Shweiki D, Itin A, Soffer D, Keshet E. Vascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenesis. Nature 1992;359:843–5.PubMedGoogle Scholar
  51. 51.
    Shima DT, Adamis AP, Ferrara N, et al. Hypoxic induction of vascular endothelial cell growth factors in the retina: Identification and characterization of vascular endothelial growth factor (VEGF) as the sole mitogen. Mol Med 1995;2:64–71.Google Scholar
  52. 52.
    Banal S, Shweiki D, Pinson A, Chandra M, Lazarovici G, Keshet E. Upregulation of vascular endothelial growth factor expression induced by myocardial ischemia: implications for coronary angiogenesis. Cardiovasc Res 1994;28:1176–9.Google Scholar
  53. 53.
    Goldberg MA, Schneider TJ. Similarities between the oxygen-sensing mechanisms regulating the expression of vascular endothelial growth factor and erythropoietin. J Biol Chem 1994;269:4355–61.PubMedGoogle Scholar
  54. 54.
    Levy AP, Levy NS, Wegner S, Goldberg MA. Transcriptional regulation of the rat vascular endothelial growth factor gene by hypoxia. J Biol Chem 1995;270:13333–40.PubMedGoogle Scholar
  55. 55.
    Madan A, Curtin PT. A 24-base pair sequence 3’ to the human erythropoietin contains a hypoxia-responsive transcriptional enhancer. Proc Natl Acad Sci USA 1993;90:3928–32.PubMedGoogle Scholar
  56. 56.
    Wang GL, Jiang BH, Rue EA, Semenza GL. Hypoxia-inducible factor-1 is a basic helix-loop helix-PAS heterodimer regulated by cellular 02 tension. Proc Natl Acad Sci USA 1995;92:5510–4.PubMedGoogle Scholar
  57. 57.
    Mukhopadhyay D, Tsilokas L, Zhou X-M, Foster D, Brugge JS, Sukhatme VP. Hypoxic induction of human vascular endothelial growth factor expression through c-Src activation. Nature 1995;375:577–81.PubMedGoogle Scholar
  58. 58.
    Frank S, Hubner G, Breier G, Longaker MT, Greenhalgh DG, Werner S. Regulation of VEGF expression in cultured keratinocytes. Implications for normal and impaired wound healing. J Biol Chem 1995;270:12607–13.PubMedGoogle Scholar
  59. 59.
    Pertovaara L, Kaipainen A, Mustonen T, et al. Vascular endothelial growth factor is induced in response to transforming growth factor-ß in fibroblastic and epithelial cells. J Biol Chem 1994;269:6271–4.PubMedGoogle Scholar
  60. 60.
    Li J, Perrella MA, Tsai JC, et al. Induction of vascular endothelial growth factor gene expression by interleukin-1 beta in rat aortic smooth muscle cells. J Biol Chem 1995;270:308–12.PubMedGoogle Scholar
  61. 61.
    Claffey KP, Wilkinson WO, Spiegelman BM. Vascular endothelial growth factor. Regulation by cell differentiation and activated second messenger pathways. J Biol Chem 1992;267:16317–22.PubMedGoogle Scholar
  62. 62.
    Kieser A, Weich H, Brandner G, Marme D, Kolch W. Mutant p53 potentiates protein kinase C induction of vascular endothelial growth factor expression. Oncogene 1994;9:963–9.PubMedGoogle Scholar
  63. 63.
    Vaisman N, Gospodarowicz D, Neufeld G. Characterization of the receptors for vascular endothelial growth factor. J Biol Chem 1990;265:19461–9.PubMedGoogle Scholar
  64. 64.
    Ploüet J, Moukadiri HJ. Characterization of the receptors to vasculotropin on bovine adrenal cortex-derived capillary endothelial cell. J Biol Chem 1990; 265:22071–5.PubMedGoogle Scholar
  65. 65.
    Thieme H, Aiello LP, Ferrara N, King GL. Comparative analysis of VEGF receptors on retinal and aortic endothelial cells. Diabetes 1995;44:98–103.PubMedGoogle Scholar
  66. 66.
    Jakeman LB, Winer J, Bennett GL, Altar CA, Ferrara N. Binding sites for vascular endothelial growth factor are localized on endothelial cells in adult rat tissues. J Clin Invest 1992;89:244–53.PubMedGoogle Scholar
  67. 67.
    Jakeman LB, Armanini M, Phillips HS, Ferrara N. Developmental expression of binding sites and mRNA for vascular endothelial growth factor suggests a role or this protein in vasculogenesis and angiogenesis. Endocriniology 1993;133:848–59.Google Scholar
  68. 68.
    deVries C, Escobedo JA, Ueno H, Houck KA, Ferrara N, Williams LT. The fms-like tyrosine kinase, a receptor for vascular endothelial growth factor. Science 1992;255:989–91.Google Scholar
  69. 69.
    Terman BI, Vermazen MD, Carrion ME, et al. Identification of the KDR tyrosine kinase as a receptor for vascular endothelial growth factor. Biochem Biophys Res Commun 1992;34:1578–86.Google Scholar
  70. 70.
    Quinn T, Peters KG, de Vries C, Ferrara N, Williams LT. Fetal liver kinase 1 is a receptor for vascular endothelial growth factor and is selectively expressed in vascular endothelium. Proc Natl Acad Sci USA 1993;90:7533–7.PubMedGoogle Scholar
  71. 71.
    Millauer B, Wizigmann-Voos S, Schnurch H, et al. High affinity binding and developmental expression suggest Flk-1 as a major regulator of vasculogenesis and angiogenesis. Cell 1993;72:835–46.PubMedGoogle Scholar
  72. 72.
    Kendell RL, Thomas KA. Inhibition of vascular endothelial growth factor by an endogenously encoded soluble receptor. Proc Natl Acad Sci USA 1993; 90:10705–9.Google Scholar
  73. 73.
    Waltenberger J, Claesson-Welsh L, Siegbahn A, Shibuya M, Heldin C-H. Different signal transduction properties of KDR and Fltl, two receptors for vascular endothelial growth factor. J Biol Chem 1994;269:26988–95.PubMedGoogle Scholar
  74. 74.
    Seetharam L, Gotoh N, Maru Y, Neufeld G, Yamaguchi S, Shibuya M. A unique signal transduction pathway for the FLT tyrosine kinase, a receptor for vascular endothelial growth factor. Oncogene 1995;10:135–47.PubMedGoogle Scholar
  75. 75.
    Fong G-H, Rassant J, Gertenstein M, Breitman M. Role of Fit-1 receptor tyrosine kinase in regulation of assembly of vascular endothelium. Nature 1995;376:66–70.PubMedGoogle Scholar
  76. 76.
    Shalabi F, Rossant J, Yamaguchi TP, et al. Failure of blood island formation and vasculogenesis in Flk-1 deficient mice. Nature 1995;376:62–6.Google Scholar
  77. 77.
    Shifren JL, Doldi N, Ferrara N, Mesiano S, Jaffe RB. In the human fetus, vascular endothelial growth factor (VEGF) is expressed in epithelial cells and myocytes, but not vascular endothelium: implications for mode of action. J Clin Endocrinol Metab 1994;79:316–22.PubMedGoogle Scholar
  78. 78.
    Monacci W, Merrill M, Oldfield E. Expression of vascular permeability factor/vascular endothelial growth factor in normal rat tissues. Am J Physiol 1993;264:C995–1002.PubMedGoogle Scholar
  79. 79.
    Ravindranath N, Little-Ihrig L, Phillips HS, Ferrara N, Zeleznick AJ. Vascular endothelial growth factor mRNA expression in the primate ovary. Endocrinology 1992;131:254–60.PubMedGoogle Scholar
  80. 80.
    Dvorak HF, Brown LF, Detmar M, Dvorak AM. Vascular permeability factor/vascular endothelial growth factor, microvascular permeability and angiogenesis. Am J Pathol 1995;146:1029–39.PubMedGoogle Scholar
  81. 81.
    Plate KH, Breier G, Weich HA, Risau W. Vascular endothelial growth is a potential tumour angiogenesis factor in vivo. Nature 1992;359:845–7.PubMedGoogle Scholar
  82. 82.
    Phillips HS, Armanini M, Stavrou D, Ferrara N, Westphal M. Intense focal expression of vascular endothelial growth factor mRNA in human intracranial neoplasms: association with regions of necrosis. Int J Oncol 1993;2:913–9.PubMedGoogle Scholar
  83. 83.
    Berkman RA, Merrill MJ, Reinhold WC, et al. Expression of the vascular permeability/vascular endothelial growth factor gene in central nervous system neoplasms. J Clin Invest 1993;91:153–9.PubMedGoogle Scholar
  84. 84.
    Wizigmann-Voss S, Breier G, Risau W, Plate K. Up-regulation of vascular endothelial growth factor and its receptors in von Hippel-Lindau disease-associated and sporadic hemangioblastoma. Cancer Res 1994;55:1358–64.Google Scholar
  85. 85.
    Warren RS, Yuan H, Matli MR, Gillett NA, Ferrara N. Regulation by vascular endothelial growth factor of human colon cancer tumorigenesis in a mouse model of experimental liver metastasis. J Clin Invest 1995;95:1789–97.PubMedGoogle Scholar
  86. 86.
    Ferrara N, Winer J, Burton T, et al. Expression of vascular endothelial growth factor does not promote transformation but confers a growth advantage in vivo to chinese hamster ovary cells. J Clin Invest 1993;91:160–70.PubMedGoogle Scholar
  87. 87.
    Kim KJ, Li B, Houck K, Winer J, Ferrara N. The vascular endothelial growth factor proteins: identification of biologically relevant regions by neutralizing monoclonal antibodies. Growth Factors 1992;7:53–64.PubMedGoogle Scholar
  88. 88.
    Millauer B, Shawver LK, Plate KH, Risau W, Ullrich A. Glioblastoma growth is inhibited in vivo by a negative dominant Flk-1 mutant. Nature 1994; 367:576–9.PubMedGoogle Scholar
  89. 89.
    Patz A. Studies on retinal neovascularization. Invest Ophthalmol Vis Sci 1980;19:1133–8.PubMedGoogle Scholar
  90. 90.
    Olk RJ, Lee CM. Diabetic retinopathy: practical management. Philadelphia: Lippincott, 1993.Google Scholar
  91. 91.
    Bauters C, Asahara T, Zheng LP, et al. Physiologic assessment of augmented vascularity induced by VEGF in a rabbit ischemic hindlimb model. Am J Physiol 1994;267:H1263–71.PubMedGoogle Scholar
  92. 92.
    Michaelson IC. The mode of development of the vascular system of the retina with some observations on its significance for certain retinal disorders. Trans Ophthalmol Sci UK 1948;68:137–80.Google Scholar
  93. 93.
    Adamis AP, Miller JW, Bernal M-T, et al. Increased vascular endothelial growth factor in the vitreous of eyes with proliferative diabetic retinopathy. Am J Ophthalmol 1994;118:445–50.PubMedGoogle Scholar
  94. 94.
    Malecaze F, Clemens S, Simorer-Pinotel V, et al. Detection of vascular endothelial growth factor mRNA and vascular endothelial growth factor-like activity in proliferative diabetic retinopathy. Arch Ophthalmol 1994;112:1476–82.PubMedGoogle Scholar
  95. 95.
    Pe’er J, Shweiki D, Itin A, Hemo I, Gnessin H, Keshet E. Hypoxia-induced expression of vascular endothelial growth factor (VEGF) by retinal cells is a common factor in neovascularization. Lab Invest 1995;72:638–45.PubMedGoogle Scholar
  96. 96.
    Adamis AP, Shima DT, Tolentino M, et al. Inhibition of VEGF prevents ocular neovascularization in a primate. Arch Ophthalmol 1996;144:66–71.Google Scholar
  97. 97.
    Aiello LP, Pierce EA, Foley ED, et al. Suppression of retinal neovascularization in vivo by inhibition of vascular endothelial growth factor (VEGF) using soluble VEGF-receptor chimeric proteins. Proc Natl Acad Sci USA. In press.Google Scholar
  98. 98.
    Koch E, Harlow L, Haines GK, et al. Vascular endothelial growth factor: a cytokine modulating endothelial function in rheumatoid arthritis. J Immunol 1994;152:4149–5.PubMedGoogle Scholar
  99. 99.
    Fava RA, Olsen NJ, Spencer-Green G, et al. Vascular permeability factor/ vascular endothelial growth factor (VPF/VEGF): accumulation and expression in human synovial fluids and rheumatoid arthritis. J Exp Med 1994;180:340–6.Google Scholar
  100. 100.
    Brown LF, Harris TJ, Yeo KT, et al. Increased expression of vascular permeability factor (vascular endothelial growth factor) in bullous pemphigoid, dermatitis herpetiformis and erythema multiforme. J Invest Dermatol 1995;104:744–9.PubMedGoogle Scholar
  101. 101.
    Lyttle DJ, Fraser KM, Flemings SB, Mercer AA, Robinson AJ. Homologs of vascular endothelial growth factor are encoded by the poxvirus orf virus. J Virol 1994;68:84–92.PubMedGoogle Scholar
  102. 102.
    Graor RA, Gray BH. Interventional treatment of peripheral vascular disease. In: Young JR, Graor RA, Olin JW, Bartholomew JR, eds. Peripheral vascular diseases. St. Louis: Mosby, 1991:111–33.Google Scholar
  103. 103.
    Takeshita S, Pu L-Q, Stein LA, et al. Intramuscular administration of vascular endothelial growth factor induces dose-dependent collateral artery augmentation in a rabbit model of chronic limb ischemia. Circulation 1994;90:II228–34.PubMedGoogle Scholar
  104. 104.
    Waler CE, Errett CJ, Ogez J, et al. Vascular endothelial growth factor (VEGF) improves blood flow and function in a chronic ischemic hind-limb model. J Cardiovasc Pharmacol 1966;27:91–8.Google Scholar
  105. 105.
    Bauters C, Asahara T, Zheng LP, et al. Recovery of disturbed endothelium-dependent flow in collateral-perfused rabbit ischemic hindlimb following administration of VEGF. Circulation 1995;91:2793–01.PubMedGoogle Scholar
  106. 106.
    Essed CD, Brand MVD, Becker AE. Transluminal coronary angioplasty and early restenosis. Br Heart J 1983;49:93–02.Google Scholar
  107. 107.
    Asahara T, Bauters C, Pastore C, et al. Local delivery of vascular endothelial growth factor accelerates re-endothelialization and attenuates intimal hyperplasia in balloon-injured rat carotid artery. Circulation 1995;91:2802–09.PubMedGoogle Scholar
  108. 108.
    Callow AD, Choi ET, Trachtenberg JD, et al. Vascular permeability factor accelerates endothelial regrowth following balloon angioplasty. Growth Factors 1994;10:223–8.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1997

Authors and Affiliations

  • Napoleone Ferrara

There are no affiliations available

Personalised recommendations