VEGF-induced mobilization of caveolae and increase in permeability of endothelial cells

Am J Physiol Cell Physiol. 2002 May;282(5):C1053-63. doi: 10.1152/ajpcell.00292.2001.


Glomerular epithelial cells (GEC) are a known site of vascular endothelial growth factor (VEGF) production. We established immortalized rat GEC, which retained the ability to produce VEGF. The isoforms expressed by GEC were defined as VEGF-205, -188, -120, and -164. The electrical resistance of endothelial cells cultured on GEC-conditioned matrix, an indicator of the permeability of monolayers to solutes, was significantly increased by the treatment with the neutralizing polyclonal antibodies to VEGF and decreased by VEGF-165. Transfection of endothelial cells with green fluorescence protein-caveolin construct and intravital confocal microscopy showed that VEGF results in a rapid appearance of transcellular elongated structures decorated with caveolin. Transmission electron microscopy of endothelial cells showed that caveolae undergo rapid internalization and fusion 30 min after application of VEGF-165. Later (36 h), endothelial cells pretreated with VEGF developed fenestrae and showed a decrease in electrical resistance. Immunoelectron microscopy of glomeruli confirmed VEGF localization to podocytes and in the basement membrane. In summary, immortalized GEC retain the ability to synthesize VEGF. Matrix-deposited and soluble VEGF leads to the enhancement of caveolae expression, their fission and fusion, formation of elongated caveolin-decorated structures, and eventual formation of fenestrae, both responsible for the increase in endothelial permeability.

Publication types

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

MeSH terms

  • Animals
  • Caveolae / metabolism*
  • Caveolae / ultrastructure
  • Caveolin 1
  • Caveolins / genetics
  • Caveolins / metabolism
  • Cells, Cultured
  • Coculture Techniques
  • Electric Capacitance
  • Endothelial Growth Factors / metabolism*
  • Endothelium, Vascular / metabolism*
  • Endothelium, Vascular / ultrastructure
  • Humans
  • Immunohistochemistry
  • Kidney Glomerulus / cytology
  • Kidney Glomerulus / metabolism*
  • Lymphokines / metabolism*
  • Membrane Potentials / physiology
  • Microscopy, Confocal
  • Permeability*
  • Protein Isoforms
  • Rats
  • Recombinant Fusion Proteins / metabolism
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors


  • CAV1 protein, human
  • Cav1 protein, rat
  • Caveolin 1
  • Caveolins
  • Endothelial Growth Factors
  • Lymphokines
  • Protein Isoforms
  • Recombinant Fusion Proteins
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors