Advertisement

Growth Factor Regulators of Placental Angiogenesis

  • Caroline Dunk
  • Asif Ahmed

Abstract

The human placenta is a highly vascularised organ that mediates gas and nutrient exchange between the maternal and fetal circulations. In this chapter we discuss the processes of vasculogenesis, angiogenesis and the factors influencing them in the formation of the placental vasculature. Also described are the effects of growth factors on the specialised structures of the mature intermediate and terminal villi, which are the main site of gas exchange. We have identified VEGF to be a key agent in early placental angiogenesis, acting in concert with a related factor, placenta growth factor (PlGF) via two high affinity receptors VEGFR-1 and VEGFR-2 to stimulate endothelial cell proliferation and vessel formation. A second class of receptor tyrosine kinases includes the Tie-2 receptor. Its newly identified ligands angiopoietin-1 and a natural antagonist angiopoietin-2 are thought to play a role in vessel maturation, acting downstream to VEGF.

Keywords

Hepatocyte Growth Factor Human Placenta Intrauterine Growth Restriction Placental Villus Growth Factor Regulator 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Demir R, Kaufmann P, Castelucci M, Erbengi T, Kotowski A. Fetal vasculogenesis and angiogenesis in human placental villi. Acta Anat (Basel) 1989:136:190–203.CrossRefGoogle Scholar
  2. Ahmed AS, Li XF, Dunk CE, Whittle MJ, Rollason T. Colocalisation of vascular endothelial growth factor and its flt-1 receptor in human placenta. Growth Factors 1995;12:235–43.PubMedCrossRefGoogle Scholar
  3. Davidoff M, Scheibler TH. Uber den Feinbau der Meerscwheinchenplacenta wahrend der Entwicklung. Anat Embryol (Berlin) 1970;130:234–54.CrossRefGoogle Scholar
  4. 4.
    King, BF. Ultrastructural differentiation of stromal and vascular components in early macaque placental villi. American Journal of Anatomy 1987;178:30–44.PubMedCrossRefGoogle Scholar
  5. 5.
    Benirschke K, Kaufmann P. Pathology of the human placenta, 3rd end. New York:Springer, 1995.Google Scholar
  6. 6.
    Kadyrov M, et al. Lancet 1999; in press [to add-JK].Google Scholar
  7. 7.
    Kohnen G, Kertschanska S, Demir R, Kaufmann P. Placental villous stroma as a model system for myofibroblast differentiation. Histochemistry and Cell Biology, 1996; 105,415–429.PubMedCrossRefGoogle Scholar
  8. 8.
    Demir R, Kosanke G, Kohen G, Kertschanka S, Kaufmann P. Classification of human placental stem villi: review of structural and functional aspects. Micros Res Tech 1997;38:29–41.CrossRefGoogle Scholar
  9. 9.
    Kaufmann P, Bruns U, Leiser R, Luckhardt M, Winterhager E. The fetal vascularisation of term human placental villi. II. Intermediate and terminal villi. Anat Embryol (Berlin) 1985;173:203–14. Google Scholar
  10. 10.
    Ferriani RA, Ahmed A, Sharkey AM, Smith SK. Colocalisation of acidic and basix fibrobast growth factor (FGF) in human placenta and the cellular effects of bFGF in trophoblast cell line JEG-3. Growth Factors 1994;10:259.PubMedCrossRefGoogle Scholar
  11. 11.
    Shams M, Ahmed A. Localisation of mRNA for basic fibroblast growth factor in human placenta. Growth Factors 1994;11:105–11.PubMedCrossRefGoogle Scholar
  12. 12.
    Crescimanno C, Marzioni D, Persico MG, Vuckovic M, Muhauser J, Castelucci M. Expression of bFGF, PlGF and their receptors in the human placenta. Placenta 1995;16:A13.Google Scholar
  13. 13.
    Sharkey AM, Charnock-Jones DS, Boocock CA, Brown KD, Smith SK. Expression of mRNA for vascular endothelial growth factor in human placenta. J Reprod Fértil 1993;99:609–15.PubMedCrossRefGoogle Scholar
  14. 14.
    Ahmed AS, Dunk CE, Kniss D, Wilkes M. Role of VEGF Receptor (Flt-1) in mediating calcium dependant nitric oxide release and limiting DNA synthesis in human trophoblast cells. Lab Invest 1997;76:779–91.PubMedGoogle Scholar
  15. 15.
    Wheeler T, Elcock CL, Anthony FW. Angiogenesis in the placental environment. Placenta 1995;16:289–96.PubMedCrossRefGoogle Scholar
  16. 16.
    Shore VH, et al. Vascular endothelial growth factor, placenta growth factor and their receptors in isolated human trophoblast. Placenta 1997;18:657–65.PubMedCrossRefGoogle Scholar
  17. 17.
    Vuorela P, et al. Expression of vascular endothelial growth factor and placenta growth factor in human placenta. Biol Reprod 1997;56:489–94.PubMedCrossRefGoogle Scholar
  18. 18.
    Khaliq A, Li XF, Shams M, Sisi P, Acevedo CA, Whittle MJ. Localisation of placenta growth factor (PlGF) in human term placenta. Growth Factors 1996; 13:243.PubMedCrossRefGoogle Scholar
  19. 19.
    Rosen EM, Meromsky L, Setter E, Vinter DW, Goldberg ID. Smooth muscle derived factor stimulates mobility of human tumour cells. Invasion Metastasis 1990;10:49–64.PubMedGoogle Scholar
  20. 20.
    Uehara Y, et al. Placental defect and embryonic lethality in mice lacking hepatocyte growth factor/scatter factor. Nature 1995;373:702–5.PubMedCrossRefGoogle Scholar
  21. 21.
    Kilby MD, et al. Localisation of hepatocyte growth factor (HGF) and its receptor (c-met) protein and mRNA in human term placenta. Growth Factors 1996;13:133–9.PubMedCrossRefGoogle Scholar
  22. 22.
    Clarke DE, Smith SK, Sharkey AM, Charnock Jones DS. Localisation of VEGF and expression of its receptors flt-1 and KDR in human placenta throughout pregnancy. Hum Reprod 1996;11:1080–98. Google Scholar
  23. 23.
    Conolly DT, et al. Human vascular permeability factor: Isolation from U937 cells. J Biol Chem 1989;264:20017–24.Google Scholar
  24. 24.
    Senger Dr, Peruzzi CA, Feder J, Dvorak HF. Tumour cells secrete a vascular permeability factor that promoted accumalation of ascites fluid. Science 1983;219:983–5. Google Scholar
  25. 25.
    Dvorak HF, Brown LF, Detmar M, Dvorak AM. Vascular permeability factor/vascular endothelial growth factor, microvascular hyperpermeability, and angiogenesis. Am J Pathol 1995;146:1029–39.PubMedGoogle Scholar
  26. 26.
    de Vries C, et al. The fms like tyrosine kinase: a receptor for vascular endothelial growth factor. Science 1992;255:989–91.PubMedCrossRefGoogle Scholar
  27. 27.
    Terman Bí, et al. Identification of KDR tyrosine kinase as a receptor for vascular endothelial growth factor. Biochem Biophys Res Commun 1992;187:1579–86.CrossRefGoogle Scholar
  28. 28.
    Millauer B, et al. High affinity vascular endothelial growth factor binding and developmental expression suggest Flk-1 as a major eregulator of vasculogenesis and angiogenesis. Cell 1993;72:835–46.PubMedCrossRefGoogle Scholar
  29. 29.
    Carmieliet P, et al. Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele. Nature 1996;380:435–9.CrossRefGoogle Scholar
  30. 30.
    Shalaby F, et al. Failure of blood island formation and vasculogenesis in flk-1 deficient mice. Nature 1995;376:62–6.PubMedCrossRefGoogle Scholar
  31. 31.
    Fong GH, Rossant J, Gersenstein M, Breitman ML. Role of the Flt-1 receptor tyrosine kinase in regulating the assembly of vascular endothelium. Nature 1995;376:66–70.PubMedCrossRefGoogle Scholar
  32. 32.
    Maglione D, et al. Isolation of a human placental cDNA coding for a protein related to the vascular permeability factor. Proc Natl Acad Sci USA 1988;88:9267–71.CrossRefGoogle Scholar
  33. 33.
    Dunk CE, Khaliq A, Ahmed AS. Oxygen modulates vascular endothelial growth factor (VEGF) secretion, trophoblast proliferation and VEGF receptor activation. Vigso, Denmark: European Placenta Group 1997.Google Scholar
  34. 34.
    Vuckovic M, et al. Expression of the vascular endothelial growth factor receptor, KDR, in human placenta. J Anat 1996;188:361–6.PubMedGoogle Scholar
  35. 35.
    Charnock-Jones DS, et al. Vascular endothelial growth factor localisation and activation in human trophoblast and choriocarcinoma cells. Biol Reprod 1994;51:524–30.PubMedCrossRefGoogle Scholar
  36. 36.
    Athanassiades A, Hamilton GS, Lala PK. Role of vascular endothelial growth factor (VEGF) in human extravillous trophoblast proliferation, migration and invasiveness. Placenta 1998;19: 465–73.PubMedCrossRefGoogle Scholar
  37. 37.
    Clauss M, et al. The vascular endothelial growth factor Fit-1 mediates biological activities: Implications for a functional role of placental growth factor in monocyte activation and Chemotaxis. J Biol Chem. 1996;271(30):17629–34.PubMedCrossRefGoogle Scholar
  38. 38.
    Holt VJ, et al. Normal human trophoblast express and respond to angiogenic growth factors. Placenta 1999;in press. Google Scholar
  39. 39.
    Conolly DT, et al. Tumour vascular permeability factor stimulates endothelial cell growth and angiogenesis. J Clin Invest 1989;84:1470–8.CrossRefGoogle Scholar
  40. 40.
    Ferrara N, Henzel WJ. Pituitary endothelial cells secrete a novel heparin binding growth factor for vasculat endothelial cells. Biochem Biophys Res Commun 1989;161:851–8.PubMedCrossRefGoogle Scholar
  41. 41.
    Plouet J, Schilling J, Gospodarowicz D. Isolation and characterisation of a newly identified endothelial cell mitogen produced by AtT-20 cells. EMBO J 1989;8:3801–6.PubMedGoogle Scholar
  42. 42.
    Yamane A, et al. A new communication system between hepatocytes and sinusoidal endothelial cells in liver through vascular endothelial growth factor and Flt-1 tyrosine kinase receptor family (Fit-1 and KDR). Oncogene 1994;9:2683–90.PubMedGoogle Scholar
  43. 43.
    Rousseau S, Huole F, Landry J, Huot J. p38 MAP kinase activation by vascular endothelial growth factor mediates actin reorganisation and cell migration in human endothelial cells. Oncogene 1997;15:2169–77.PubMedCrossRefGoogle Scholar
  44. 44.
    Mandriota SJ, et al. Vascular endothelial frowth factor increases urokinase receptor expression of vascular endothelial cells. J Biol Chem 1995;270(17):9709–16.PubMedCrossRefGoogle Scholar
  45. 45.
    Hauser S, Weich HA. A heparin-binding form of placenta growth factor (PlGF-2) is expressed in human umbilical vein endothelial cells and in placenta. Growth Factors 1993;9:259–68.PubMedCrossRefGoogle Scholar
  46. 46.
    Birkenhager R, et al. Synthesis and physiological activity of heterodimers comprising different splice forms of vascular endothelial growth factor and placenta growth factor. Biochem J 1996;3126:703–7.Google Scholar
  47. 47.
    Keck PJ, et al. Vascular permeability factor, an endothelial mitogen related to PDGF. Science 1989;246:1309–12.PubMedCrossRefGoogle Scholar
  48. 48.
    Park JE, Chen HH, Winer J, Houck KA, 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-l/KDR. J Biol Chem 1994;269:25646–54.PubMedGoogle Scholar
  49. 49.
    Wilting J, et al. Vascular endothelial growth factor (VEGF) and placenta growth factor (P1GF): homologous factors specifically affecting endothelial ells. Ann Anat 1995;178:331A.Google Scholar
  50. 50.
    Wilting J, et al. VEGF(121) induces proliferation of vascular endothelial cells and expression of Flk-1 without affecting lymphatic vessels of the chorioallantoic membrane. Dev Biol 1996;176:76–85.PubMedCrossRefGoogle Scholar
  51. 51.
    Jackson MR, Carney EW, Lye S J, Ritchie JW. Localisation of two angiogenic growth factors (PDECGF and VEGF) in human placentae throughout gestation. Placenta 1994;15:341–53. Google Scholar
  52. 52.
    Shiraishi S, Nakagawa K, Kinukawa N, Nakano H, Sueishi K. Immunohistochemical localisation of vascular endothelial growth factor in the human placenta. Placenta 1996; 17:111–21.PubMedCrossRefGoogle Scholar
  53. 53.
    Leiser R, Luckhardt M, Kaufmann P, Winterhager E, Bruns U. The fetal vascularisation of term human placental villi. I. Peripheral stem villi. Ana Embryol (Berlin) 1985;173:71–80.Google Scholar
  54. 54.
    Watanabe Y, Dvorak HF. Vascular permeability factor/vascular endothelial growth factor inhibits anchorage dependent apopotosis in microvessel endothelial cells by inducing scaffold formation. Exp Cell Res 1997;233:340–9.PubMedCrossRefGoogle Scholar
  55. 55.
    Waltenberger J, et al. Different signal transduction properties of KDR and Flt-1, two receptors for vascular endothelial growth factor. J Biol Chem 1994;269:26988–95.PubMedGoogle Scholar
  56. 56.
    Dunk C, Ahmed A. Expression of VEGF-C and activation of its receptors VEGR-2 and VEGFR-3 in placenta: decreased expression in IUGR. Lab Invest 1999;in press. Google Scholar
  57. 57.
    Brock TA, Dvorak HF, Senger DR. Tumour secreted vascular permeability factor increases cytosolic Ca2+ and von Willebrand factor in human endothelial cells. Am J Pathol 1991;138: 213–21.PubMedGoogle Scholar
  58. 58.
    Seymour LW, et al. Vascular endothelial growth factor stimulates protein kinase C dependant pospholipase D activity in endothelial cells. Lab Invest 1996;75:427–37.PubMedGoogle Scholar
  59. 59.
    van der Zee R, et al. Vascular endothelial growth factor (VEGF)/vascular permeability factor (VPF) augments nitric oxide release from quiescent rabbit and human vascular endothelium. Circulation 1997;95:1030–7.PubMedGoogle Scholar
  60. 60.
    Nanaev A, Chwalisz K, Frank H, Kohnen G, Hegele-Hartung C, and Kaufmann P. Physiological dilation of uteroplacental arteries in the guinea pig depends on nitric oxide synthase activity of extra villous trophoblast. Cell Tissue Res 1995;282:407–21.PubMedCrossRefGoogle Scholar
  61. 61.
    Garg UC, Hassid A. Nitric oxide generating vasodilators and 8-bromo-cyclic guanosine monophosphate inhibit mitogenesis and proliferation of cultured rat vascular smooth muscle cells. J Clin Invest 1989;83:1774–7.PubMedCrossRefGoogle Scholar
  62. 62.
    Gooch KJ, Dangler CA, Frangos JA. Exogenous, basal, and flow induced nitric oxide production and endothelial cell proliferation. J Cell Physiol 1997;171:252–8.PubMedCrossRefGoogle Scholar
  63. 63.
    Tsurumi Y, et al. Reciprocal regulation between VEGF and NO in the regulation of endothelial integrity. Nat Med 1997;3(8):879–86.PubMedCrossRefGoogle Scholar
  64. 64.
    Dumont DJ, et al. Dominant-negative and targeted null mutations in the endothelial receptor tyrosine kinase, tek, reveal and critical role in vasculogenesis of the embryo. Genes Dev 1994;8:1897–909.PubMedCrossRefGoogle Scholar
  65. 65.
    Puri MC, Rossant J, Alitalo K, Bernstein A, Partanen J. The receptor tyrosine kinase TIE is required for integrity and survival of vascular endothelial cells. EMBO J 1995;14:5884–91.PubMedGoogle Scholar
  66. 66.
    Sato TN, et al. Distinct roles of the receptor tyrosine kinases Tie-1 and Tie-2 in blood vessel formation. Nature 1995;376:70–4.PubMedCrossRefGoogle Scholar
  67. 67.
    Suri C, et al. Requisite role of angiopoietin-1, a ligand for the Tie-2 receptor, during embryonic angiogenesis. Cell 1996;87:1171–80.PubMedCrossRefGoogle Scholar
  68. 68.
    Davis S, et al. Isolation of angiopoietin-1, a ligand for the TIE2 receptor, by secretion-trap expression cloning. Cell 1996;87:1161–69.PubMedCrossRefGoogle Scholar
  69. 69.
    Schweiki D, Itin A, Neufeld G, Gitay-Goren H, Keshet E. Vascular endothelial growth factor induced by hypoxia may mediate hypoxia initiated angiogenesis. Nature 1992;359:843–5.CrossRefGoogle Scholar
  70. 70.
    Plate KH, Brier G, Weich HA, Risau W. Vascular endothelial growth factor is a potential tumour angiogenesis factor in human gliomas in vivo. Nature 1992;359:845–8.PubMedCrossRefGoogle Scholar
  71. 71.
    Brown LF, et al. Increased expression of vascular permeability factor (vascular endothelial growth factor) and receptors in kidney and bladder carcinomas. Cancer Res. 1993;59:4727–35.Google Scholar
  72. 72.
    Brown LF, et al. Increased expression of vascular permeability factor (vascular endothelial growth factor) and receptors in adenocarcinomas and gastrointestinal carcinomas. Am J Pathol 1993;143:1255–62.PubMedGoogle Scholar
  73. 73.
    Takaihashi Y, et al. Markedly increased amounts of mRNA for vascular endothelial growth factor and placenta growth factor in renal cell carcinomas associated with angiogenesis. Oncogene 1994;9:273–9.Google Scholar
  74. 74.
    Stavri G, Zachary I, Baskerville P, Martin J, Erusalimsky J. Basic fibroblast growth factor up- regulates the expression of vascular endothelial growth factor in vascular smooth muscle cells. Synergistic interaction with hypoxia. Circulation 1995;92:5–8.Google Scholar
  75. 75.
    Tuder RM, Flook BE, Voelkel NF. Increased gene expression for VEGF and the VEGF receptors KDR/Flk-1 and Fit-1 in lungs exposed to chronic hypoxia: modulation of gene expression by nitric oxide. J Clin Invest 1995;95:1798–1807.PubMedCrossRefGoogle Scholar
  76. 76.
    Rodesch F, Simon P, Donna C, Jauniaux E. Oxygen measurements in endometrial and trophoblastic tissues during early pregnancy. Obstet Gynecol 1992;80:283–5.PubMedGoogle Scholar
  77. 77.
    Kingdom JCP, Kaufmann P. Oxygen and placental villous development: origins of fetal hypoxia. Placenta 1997;18:613–21.PubMedCrossRefGoogle Scholar
  78. 78.
    Krebs C, Longo LD, Leiser D. Term ovine placental vasculature: comparison of sea level and high altitude conditions by corrosion cast and histomorphometry. Placenta 1997;18:43–51.PubMedCrossRefGoogle Scholar
  79. 79.
    Kiserud T, Hellevik LR, Eik-Nes SH, Angelsen BA, Blaas HG. Estimation of the pressure gradient across the fetal ductus venosus based on Doplar velocimetry. Ultrasound Med Biol 1994;20:225–32.PubMedCrossRefGoogle Scholar
  80. 80.
    Hitschold T, Mutefering H, Ulrich S, Berle P. Does extremely low fetoplacental impedance is estimated by umbilical artery Doppler velocimetry also indicate fetuses at risk? Ultrasound Gynecol 1996;8:39A.Google Scholar
  81. 81.
    Khaliq A, Dunk C, Jiang J. et al. Hypoxia downregulates placenta growth factor, whereas fetal growth restriction unregulates placenta growth factor expression. Molecular evidence for placental hyperoxia in intrauterine growth restriction. Lab Invest 1999; 79:151–70.Google Scholar
  82. 82.
    Macara LM, et al. Structural analysis of placental terminal villi from growth-restricted pregnancies with abnormal umbilical artery Doppler waveforms. Placenta 1996;17:37–48.PubMedCrossRefGoogle Scholar
  83. 83.
    Ahmed A, Kilby M. Hypoxia or hyperoxia in placental insufficiency. Lancet 1997;350:70–1.CrossRefGoogle Scholar

Copyright information

© Springer-Verlag London Limited 2000

Authors and Affiliations

  • Caroline Dunk
  • Asif Ahmed

There are no affiliations available

Personalised recommendations