Interaction of vasculotropin/vascular endothelial cell growth factor with human umbilical vein endothelial cells: binding, internalization, degradation, and biological effects

J Cell Physiol. 1991 Oct;149(1):50-9. doi: 10.1002/jcp.1041490108.


Vasculotropin/vascular endothelial cell growth factor (VAS/VEGF) is a newly purified growth factor with a unique specificity for vascular endothelial cells. We have investigated the interactions of VAS/VEGF with human umbilical vein endothelial cells (HUVE cells). 125I-VAS/VEGF was found to HUVE cells in a saturable manner with a half-maximum binding at 2.8 ng/ml. Scatchard analysis did show two classes of high-affinity binding sites. The first class displayed a dissociation constant of 9 pM with 500 sites/cell. The dissociation constant and the number of binding sites of the second binding class were variable for different HUVE cell cultures (KD = 179 +/- 101 pM, 5,850 +/- 2,950 sites/cell). Half-maximal inhibition of 125I-VAS/VEGF occurred with a threefold excess of unlabeled ligand. Basic fibroblast growth factor (bFGF) and heparin did not compete with 125I-VAS/VEGF binding. In contrast, suramin and protamin sulfate completely displaced 125I-VAS/VEGF binding from HUVE cells. VAS/VEGF was shown to be internalized in HUVE cells. Maximum internalization (55% of total cell-associated radioactivity) was observed after 30 min. 125I-VAS/VEGF was completely degraded 2-3 hr after binding. At 3 hr, the trichloroacetic acid (TCA)-soluble radioactivity accumulated in the medium was 60% of the total radioactivity released by HUVE cells. No degradation fragment of 125I-VAS/VEGF was observed. Chloroquine completely inhibited degradation. VAS/VEGF was able to induce angiogenesis in vitro in HUVE cells. However, it did not significantly modulate urokinase-type plasminogen activator (u-PA), tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor (PAI-1), and tissue factor (TF). Prostacyclin production was only stimulated at very high VAS/VEGF concentrations. Taken together, these results indicate that VAS/VEGF might be a potent inducer of neovascularization resulting from a direct interaction with endothelial cells. The angiogenic activity seems to be independent of the plasminogen activator or inhibitor system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cells, Cultured
  • Endothelial Growth Factors / metabolism*
  • Endothelial Growth Factors / pharmacology
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / metabolism*
  • Epoprostenol / metabolism
  • Growth Substances / metabolism*
  • Growth Substances / pharmacology
  • Humans
  • Kinetics
  • Lymphokines / metabolism*
  • Lymphokines / pharmacology
  • Neovascularization, Pathologic
  • Plasminogen Inactivators / metabolism
  • Thromboplastin / metabolism
  • Tissue Plasminogen Activator / metabolism
  • Umbilical Veins
  • Urokinase-Type Plasminogen Activator / metabolism
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors


  • Endothelial Growth Factors
  • Growth Substances
  • Lymphokines
  • Plasminogen Inactivators
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Thromboplastin
  • Epoprostenol
  • Tissue Plasminogen Activator
  • Urokinase-Type Plasminogen Activator