Angiogenic factors and their assay: activity of formyl methionyl leucyl phenylalanine, adenosine diphosphate, heparin, copper, and bovine endothelium stimulating factor

Microvasc Res. 1983 Nov;26(3):323-38. doi: 10.1016/0026-2862(83)90080-8.


A number of chemically unrelated substances have been compared for their neovasculogenic activity by two different in vivo tests, and for their ability to induce cultured endothelial cell migration and proliferation. Formyl methionyl leucyl phenylalanine, copper ions, heparin, adenosine diphosphate, and low-molecular-weight bovine endothelium stimulating factor were all neovasculogenic by the corneal pocket assay. By the chorioallantoic membrane assay, copper ions and formyl methionyl leucyl phenylalanine were not detectably neovasculogenic. By the same assay it has been possible to demonstrate angiogenic activity in bovine endothelium stimulating factor that is distinguishable from copper ions. This bovine factor, in contrast to the other agents, induced marked endothelial cell migration and also proliferation and may belong to a special class of agents which represents direct acting angiogenic activity.

MeSH terms

  • Adenosine Diphosphate / pharmacology*
  • Allantois / blood supply
  • Angiogenesis Inducing Agents / analysis
  • Animals
  • Cattle
  • Cell Division / drug effects
  • Cell Movement / drug effects
  • Chemotactic Factors / pharmacology
  • Chick Embryo
  • Copper / pharmacology*
  • Cornea / blood supply
  • Endothelium / cytology
  • Heparin / pharmacology*
  • N-Formylmethionine Leucyl-Phenylalanine / pharmacology*
  • Neovascularization, Pathologic / chemically induced*
  • Rabbits
  • Tissue Extracts / pharmacology*


  • Angiogenesis Inducing Agents
  • Chemotactic Factors
  • Tissue Extracts
  • N-Formylmethionine Leucyl-Phenylalanine
  • Adenosine Diphosphate
  • Copper
  • Heparin