In vivo angiogenic activity and hypoxia induction of heterodimers of placenta growth factor/vascular endothelial growth factor

J Clin Invest. 1996 Dec 1;98(11):2507-11. doi: 10.1172/JCI119069.


To investigate the in vivo angiogenic activity of placenta growth factor (PIGF) and its heterodimers with vascular endothelial growth factor (VEGF), the induction of neovascularization of these factors in the mouse cornea was studied. VEGF165 is sufficiently potent to stimulate new capillary growth from the limbal vessels. PIGF129/VEGF165 heterodimers also induce corneal neovascularization with a maximal vessel length similar to VEGF165, but with a marked decrease of vessel density. In contrast, PIGF129 has little or no effect in this in vivo angiogenesis assay. The expression of VEGF mRNA and protein is drastically up-regulated by hypoxia in choriocarcinoma cells, whereas expression of PIGF is not affected by the low concentration of oxygen. Up-regulation of VEGF production results in increased formation of PIGF/VEGF heterodimers in these tumor cells. Thus, hypoxia indirectly up-regulates expression levels of PIGF/VEGF heterodimers and modulates VEGF activity when these factors are co-expressed.

Publication types

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

MeSH terms

  • Angiogenesis Inducing Agents / pharmacology
  • Animals
  • Capillaries / drug effects
  • Capillaries / physiology*
  • Carcinoma, Hepatocellular
  • Cell Hypoxia
  • Cell Line
  • Choriocarcinoma
  • Cornea
  • Dimerization
  • Endothelial Growth Factors / biosynthesis*
  • Endothelial Growth Factors / pharmacology*
  • Female
  • Humans
  • Liver Neoplasms
  • Lymphokines / biosynthesis*
  • Lymphokines / pharmacology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neovascularization, Physiologic* / drug effects
  • Placenta Growth Factor
  • Pregnancy
  • Pregnancy Proteins / biosynthesis*
  • Pregnancy Proteins / pharmacology*
  • RNA, Messenger / biosynthesis
  • Recombinant Proteins / pharmacology
  • Retinal Vessels / drug effects
  • Retinal Vessels / physiology*
  • Transcription, Genetic
  • Tumor Cells, Cultured
  • Uterine Neoplasms
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors


  • Angiogenesis Inducing Agents
  • Endothelial Growth Factors
  • Lymphokines
  • PGF protein, human
  • Pgf protein, mouse
  • Pregnancy Proteins
  • RNA, Messenger
  • Recombinant Proteins
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Placenta Growth Factor