Pharmacokinetics and distribution of heparin-binding growth factor I (endothelial cell growth factor) in the rat

Circ Res. 1989 Feb;64(2):227-34. doi: 10.1161/01.res.64.2.227.


Heparin-binding growth factor I (HBGF I), previously designated as endothelial cell growth factor, is a potent mitogen for endothelial cells in vitro, which may prove useful for promoting endothelial regeneration in vivo. Analysis of the pharmacokinetics and organ distribution of HBGF I is necessary before use of HBGF I as a pharmacological agent. Consequently, pharmacological studies were carried out with [125I]HBGF I in the rat. Intravenous injections of HBGF I were given with or without heparin (2.5 units/ng HBGF I). Blood concentrations of HBGF I decreased by one half 17 seconds after HBGF I bolus. This time was prolonged to 60 seconds when HBGF I was injected with heparin. The elimination half-life of HBGF I was 14 minutes in the presence of heparin. The highest concentrations of HBGF I following intravenous bolus were found in kidney, liver, and spleen, and the lowest in fat and brain. Heparin increased HBGF I concentrations in blood and all organs measured except kidney, which was significantly decreased (p less than 0.01). Intact HBGF I was recoverable from blood 5 minutes following intravenous administration. HBGF I underwent near-complete proteolytic digestion after more prolonged ex vivo incubation with rat plasma, but HBGF I was protected from proteolysis when incubations were conducted in the presence of heparin. Thus, it is feasible that HBGF I can be administered as a pharmacological agent in the presence of heparin. Further studies assessing acceleration of in vivo endothelial growth using HBGF I with heparin appear warranted.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cells, Cultured
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / drug effects
  • Fibroblast Growth Factor 1
  • Gamma Rays
  • Growth Substances / metabolism
  • Growth Substances / pharmacokinetics*
  • Growth Substances / pharmacology
  • Heparin / metabolism
  • Heparin / pharmacokinetics*
  • Heparin / pharmacology
  • Iodine Radioisotopes
  • Male
  • Mitogens / pharmacology
  • Radiography
  • Rats
  • Rats, Inbred Strains
  • Time Factors
  • Tissue Distribution


  • Growth Substances
  • Iodine Radioisotopes
  • Mitogens
  • Fibroblast Growth Factor 1
  • Heparin