Growth Factor Control of Wound Healing Angiogenesis

  • D. R. Knighton
  • V. D. Fiegel
  • G. D. Phillips


Angiogenesis is a fundamental biologic process which plays a pivotal role in development, pathologic states and physiologic responses. In the developing embryo, blood vessels form by two mechanisms: (1) vasculogenesis, in which mesoderm-derived angioblasts migrate to specific sites in the embryo and form a network of vascular cords, and (2) angiogenesis, which occurs primarily during organogenesis, and is characterized by the sprouting of new vessels from the established cords into previously avascular organ rudiments [1, 2]. Soluble angiogenesis factor or factors deposited in the extracellular matrix may act to stimulate and direct this neovascularization.


Corpus Luteum Capillary Endothelial Cell Corneal Neovascularization Angiogenesis Factor Vascular Permeability Factor 
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.


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  1. 1.
    Poole TJ, Coffin JD (1989) Vasculogenesis and angiogenesis: two distinct morphogenetic mechanisms establish embryonic vascular pattern. J Exp Zool 251:224–231.PubMedCrossRefGoogle Scholar
  2. 2.
    Risau W, Lemmon V (1988) Changes in the vascular extracellular matrix during embryonic vasculogenesis and angiogenesis. Dev Biol 125:441–450.PubMedCrossRefGoogle Scholar
  3. 3.
    Folkman J (1974) Tumor angiogenesis. Adv Cancer Res 10:331–358.CrossRefGoogle Scholar
  4. 4.
    Moscatelli D, Joseph-Silverstein J, Presta M, Rifkin DB (1988) Multiple forms of an angiogenesis factor: basic fibroblast growth factor. Biochimie 70:83–87.PubMedCrossRefGoogle Scholar
  5. 5.
    Baird A, Walicke PA (1989) Fibroblast growth factors. Br Med Bull 45:438–452.PubMedGoogle Scholar
  6. 6.
    Keck PJ, Hauser SD, Krivi G, Sanzo K, Warren T, Feder J, Connolly DT (1989) Vascular permeability factor, an endothelial cell mitogen related to PDGF. Science 246:1309–1312.PubMedCrossRefGoogle Scholar
  7. 7.
    Ziche M, Jones J, Gullino PM. (1982) Role of prostaglandin E1 and copper in angiogenesis. JNCI 69:475–482.PubMedGoogle Scholar
  8. 8.
    Weiss JB, Brown RA, Kumar S, Phillips P (1979) An angiogenic factor isolated from tumours. A potent low molecular weight compound. Br J Cancer 40:493–496.PubMedCrossRefGoogle Scholar
  9. 9.
    Fett JW, Strydom DJ, Lobb RR, Alderman EM, Bethune JL, Riordan JF, Vallee BL (1985) Isolation and characterization of angiogenin, an angiogenic protein from human carcinoma cells. Biochemistry 24:5480–5486.PubMedCrossRefGoogle Scholar
  10. 10.
    Redmer DA, Grazul AT, Kirsch JD, Reynolds LP (1988) Angiogenic activity of bovine corpora lutea at several stages of luteal development. J Reprod Ferti 82:627–634.CrossRefGoogle Scholar
  11. 11.
    Gospodarowicz D, Thakral KK (1977) Production of a corpus luteum angiogenic factor responsible for proliferation of capillaries and neovascularization of the corpus luteum. Proc Natl Acad Sci, USA 75:847–851.CrossRefGoogle Scholar
  12. 12.
    Reynolds LP, Millaway DS, Kirsch JD, Infeld JE, Redmer DA (1987) Angiogenic activity of placental tissues of cows. J Reprod Ferti 81:233–240.CrossRefGoogle Scholar
  13. 13.
    Reynolds LP, Reder DA (1988) Secretion of angiogenic activity by placental tissues of cows at several stages of gestation. J Reprod Ferti 83:497–502.CrossRefGoogle Scholar
  14. 14.
    Burgos H (1986) Angiogenic factor from human term placenta. Purification and partial characterization. Eur J Clin Invest 16:486–493.PubMedCrossRefGoogle Scholar
  15. 15.
    Moscatelli D, Presta M, Rifkin DB (1986) Purification of a factor from human placenta that stimulates capillary endothelial cell protease production, DNA synthesis, and migration. Proc Natl Acad Sci USA 83:2091–2095.PubMedCrossRefGoogle Scholar
  16. 16.
    Phillips GD, Fiegel VD, Knighton DR (1992) Putative angiogenesis factors: A review. Wounds 4:94–107.Google Scholar
  17. 17.
    Ausprunk DH, Folkman J (1977) Migration and proliferation of endothelial cells in preformed and newly formed blood vessels during tumor angiogenesis. Microvasc Res 14:53–65.PubMedCrossRefGoogle Scholar
  18. 18.
    Burger PC, Chandler DB, Klintworth GK (1983) Corneal neovascularization as studied by scanning electron microscopy of vascular casts. Lab Invest 48:169–180.PubMedGoogle Scholar
  19. 19.
    Burger PC, Chandler DB, Klintworth GK (1984) Scanning electron microscopy of vascular casts. J Electron Microsc Techn 1:341–348.CrossRefGoogle Scholar
  20. 20.
    Phillips GD, Whitehead RA, Knighton DR (1991) Inititation and pattern of angiogenesis in wound healing in the rat. Am J Anat 192:257–262.PubMedCrossRefGoogle Scholar
  21. 21.
    Knighton DR, Fiegel VD, Austin LL, Ciresi KF, Butler EL (1986) Classification and treatment with autologous platelet-derived wound healing factors (PDWHF). Ann Surg 204:322–330.PubMedCrossRefGoogle Scholar
  22. 22.
    Roberts A, Sporn MB, Assoian RK, Smith JM, Roche NS, Wakefield LM, Heine UI, Liotta LA, Falanga V, Kehrl JH, Fauci AS (1986) Transforming growth factor type B: rapid induction of fibrosis and angiogenesis in vivo and stimulation of collagen formation in vitro. Proc Natl Acad Sci USA 83:4167–4171.PubMedCrossRefGoogle Scholar
  23. 23.
    Gimbrone MA Jr, Cotran R, Leapman SB, Folkman J (1974) Tumor growth and neovas-cularization: an experimental model using the rabbit cornea JNCI 52:413–427.PubMedGoogle Scholar
  24. 24.
    Phillips GD, Whitehead RA, Stone AM, Ruebel MW, Goodkin ML, Knighton DR (1994) Transforming growth factor beta (TGF-β) stimulation of angiogenesis: an electron microscopic study. J Submicrosc Cytol Pathol 25:149–155.Google Scholar
  25. 25.
    Phillips GD, Whitehead RA, Knighton DR (1992) Inhibition by methylprednisolone acetate suggests an indirect mechanism for TGF-B induced angiogenesis. Growth Factors 6:77–84.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1995

Authors and Affiliations

  • D. R. Knighton
    • 1
  • V. D. Fiegel
    • 1
  • G. D. Phillips
    • 1
  1. 1.Institute for Reparative Medicine and Embro CorporationSt. Louis ParkUSA

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