VEGF contributes to postnatal neovascularization by mobilizing bone marrow-derived endothelial progenitor cells

EMBO J. 1999 Jul 15;18(14):3964-72. doi: 10.1093/emboj/18.14.3964.

Abstract

Vascular endothelial growth factor (VEGF) has been shown to promote neovascularization in animal models and, more recently, in human subjects. This feature has been assumed to result exclusively from its direct effects on fully differentiated endothelial cells, i.e. angiogenesis. Given its regulatory role in both angiogenesis and vasculogenesis during fetal development, we investigated the hypothesis that VEGF may modulate endothelial progenitor cell (EPC) kinetics for postnatal neovascularization. Indeed, we observed an increase in circulating EPCs following VEGF administration in vivo. VEGF-induced mobilization of bone marrow-derived EPCs resulted in increased differentiated EPCs in vitro and augmented corneal neovascularization in vivo. These findings thus establish a novel role for VEGF in postnatal neovascularization which complements its known impact on angiogenesis.

Publication types

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

MeSH terms

  • Animals
  • Bone Marrow Cells / cytology*
  • Bone Marrow Cells / drug effects
  • Bone Marrow Transplantation
  • Cell Count / drug effects
  • Cell Movement / drug effects
  • Cells, Cultured
  • Chemotaxis / drug effects
  • Cornea / cytology
  • Cornea / drug effects
  • Corneal Injuries
  • Corneal Neovascularization*
  • DNA / biosynthesis
  • Endothelial Growth Factors / pharmacology*
  • Endothelium, Vascular / cytology*
  • Endothelium, Vascular / drug effects
  • Flow Cytometry
  • Humans
  • Leukocytes, Mononuclear / cytology
  • Leukocytes, Mononuclear / drug effects
  • Lymphokines / pharmacology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Stem Cells / cytology*
  • Stem Cells / drug effects
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors

Substances

  • Endothelial Growth Factors
  • Lymphokines
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • DNA