Angiogenesis pp 129-135 | Cite as

Modulation of Vascular Endothelial Growth Factor Angiogenic Activity by ADP-Ribosylation

  • John J. Feng
  • Q. Perveen Ghani
  • Gabriel Ledger
  • Rahmat Barkhordar
  • Thomas K. Hunt
  • M. Zamirul Hussain
Part of the NATO ASI Series book series (NSSA, volume 298)


Angiogenesis is a complex series of interdependent events which basically involves Chemotaxis, proteolytic digestion of extracellular matrix, cell proliferation, vascular tube formation, anastomoses with other vascular sprouts, and cell-cell, and cell-matrix adhesion. Studies on angiogenesis have revealed that these processes are regulated by a balance of positive and negative inducers of which cytokines and growth factors are the primary stimulators (1–3). Research over the last few years have indicated the pivotal role of vascular endothelial growth factor (VEGF) in the regulation of normal and abnormal angiogenesis (3). Because of the specificity of VEGF for endothelial cell migration, proliferation and tube formation, VEGF is considered to be a major stimulus for wound angiogenesis.


Vascular Endothelial Growth Factor Cholera Toxin Endothelial Cell Migration Angiogenic Activity Broad Response 
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.
    Battegay E.J. Angiogenesis: mechanistic insights, neovascular diseases, and therapeutic prospects. J Mol Med 1995; 73, 333–346.PubMedCrossRefGoogle Scholar
  2. 2.
    Folkman J. Angiogenesis. J Biol Chem 1992: 267, 10931–10934.PubMedGoogle Scholar
  3. 3.
    Ferrara N, Davis-Smyth T. The biology of vascular endothelial growth factor. Endocrine Reviews 1997;18(l):4–25.PubMedCrossRefGoogle Scholar
  4. 4.
    Leibovich S.J. Presented at 1997 Gordon Conf on Angiogenesis. Google Scholar
  5. 5.
    Shweiki D, Neeman M., Itin A, Keshet E. Induction of vascular endothelial growth factor expression by hypoxia and by glucose deficiency in multicell spheroids: implications for tumor angiogenesis. Proc Natl Acad Sci USA 1995;92(3):768–72.PubMedCrossRefGoogle Scholar
  6. 6.
    Okazaki IJ, Moss J. Mono-ADP-ribosylation: A reversible post-translational modification of proteins. Adv Pharm 1996;35:247–280.CrossRefGoogle Scholar
  7. 7.
    Gimbrone M., Cotran R, Leapman S. and Folkman J. Tumor growth and neovascularization: An experimental model using the rabbit cornea. J Natl Cancer Inst 1974; 52: 413–416.PubMedGoogle Scholar
  8. 8.
    Knighton DR, Hunt TK, Scheuentuhl H, Halliday BJ, Werb Z, Banda MJ. Oxygen tension regulates the expression of angiogenesis factor by macrophages. Science 1983; 221: 1283–1285.PubMedCrossRefGoogle Scholar
  9. 9.
    Constant J, Suh DY, Hussain MZ, Hunt TK. Wound healing angiogenesis: The metabolic basis of repair. In: Maragoudakis ME, editor. Molecular, Cellular, and Clinical Aspects of Angiogenesis. New York: Plenum Press, 1996:151–159.CrossRefGoogle Scholar
  10. 10.
    Kleinman HK, McGarvey ML, Hassel JR, Star VL, Cannon FB, Lauri JW, Martin GR. Basement complexes with biological activity. Biochemistry 1986; 25:312–318.PubMedCrossRefGoogle Scholar
  11. 11.
    Passaniti A, Taylor RM, Pili R, Guo Y, Long PV, Haney JA, Pauly RR, Grant DS, Martin GR. A simple quantitative method for assessing angiogenesis and antiangiogenic agents using reconstituted basement membrane, heparin, and fibroblast growth factor. Lab Invest 1992; 67: 519–528.PubMedGoogle Scholar
  12. 12.
    Grant DS, Lelkes PI, Fukuda K, Kleinman HK. Intracellular mechanisms involved in basement membrane induced blood vessel differentiation in vitro. In Vitro Cell Dev Biol 1991; 27a: 327–336.CrossRefGoogle Scholar
  13. 13.
    Althaus FR, and Richter C. Mono-ADP-ribosylation Reactions: The bond, in ADP-Ribosylation of Proteins, Enzymology and Biological Significance, (Althaus FR and Richter C., eds), Springer-Verlag, New York, 1987; pp 216–220.CrossRefGoogle Scholar
  14. 14.
    Zabel DD, Feng JJ, Scheuenstuhl H, Hunt TK, Hussain MZ. Lactate stimulation of macrophage-derived angiogenic activity is associated with inhibition of poly(ADP-ribose) synthesis. Lab Invest 1996;74:644–649.PubMedGoogle Scholar
  15. 15.
    Walter DH, Hink U, Asahara T, Van Belle E, Horowitz J, Tsurumi Y, et al. The in vivo bioactivity of vascular endothelial growth factor/vascular permeability factor is independent of N-linked glycosylation. Lab Invest 1996;74(2):546–56.PubMedGoogle Scholar
  16. 16.
    Peretz D, Gitay GH, Safran M., Kimmel N, Gospodarowicz D, Neufeld G. Glycosylation of vascular endothelial growth factor is not required for its mitogenic activity. Biochem Biophys Res Commun 1992; 182(3): 1340–7.PubMedCrossRefGoogle Scholar
  17. 17.
    Trepel JB, Chuang DM, and Neff NH. Polypeptide hormones and chromatin-associated proteins act as acceptors for cholera toxin-catalyzed ADP-ribosylation. J Neurochem 1981; 36: 538–543.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1998

Authors and Affiliations

  • John J. Feng
    • 2
  • Q. Perveen Ghani
    • 1
  • Gabriel Ledger
    • 1
  • Rahmat Barkhordar
    • 1
  • Thomas K. Hunt
    • 2
  • M. Zamirul Hussain
    • 1
  1. 1.Departments of Restorative DentistryUniversity of CaliforniaSan FranciscoUSA
  2. 2.Departments of SurgeryUniversity of CaliforniaSan FranciscoUSA

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