The vascular endothelial growth factor VEGF165 induces perlecan synthesis via VEGF receptor-2 in cultured human brain microvascular endothelial cells

Biochim Biophys Acta. 2006 Sep;1760(9):1465-74. doi: 10.1016/j.bbagen.2006.06.010. Epub 2006 Jul 7.


A member of the vascular endothelial growth factor (VEGF) family, VEGF165, regulates vascular endothelial cell functions in autocrine and paracrine fashions in microvessels. Proteoglycans are highly glycosylated poly-anionic macromolecules that influence cellular behaviors such as proliferation and migration by interacting with cytokines/growth factors. In the present study, we investigated the regulation of proteoglycan synthesis by VEGF165 in cultured human brain microvascular endothelial cells. The cells were exposed to recombinant human VEGF165, and the proteoglycans were then characterized using biochemical techniques. VEGF165 treatment increased the accumulation of proteoglycans 1.4- and 1.6-fold in the cell layer and conditioned medium, respectively. This effect resulted from the activation of VEGFR-2, and was mimicked by vammin, a VEGFR-2 ligand from snake venom but not placenta growth factor, which binds specifically to VEGFR-1. VEGF165 stimulated the production and secretion of perlecan, substituted with shorter heparan sulfate side chains, but with unaltered sulfated disaccharide composition. The perlecan secreted by VEGF165-stimulated endothelial cells may be involved in the regulation of cellular behavior during angiogenesis, in diseases of the brain microvessels, and in the maintenance of the endothelial cell monolayer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain / drug effects*
  • Brain / metabolism*
  • Carbohydrate Metabolism
  • Cells, Cultured
  • Endothelial Cells / drug effects*
  • Endothelial Cells / metabolism*
  • Heparan Sulfate Proteoglycans / biosynthesis*
  • Heparan Sulfate Proteoglycans / genetics
  • Humans
  • Microcirculation / drug effects
  • Microcirculation / metabolism
  • RNA, Messenger / genetics
  • Vascular Endothelial Growth Factor A / pharmacology*
  • Vascular Endothelial Growth Factor Receptor-2 / metabolism*


  • Heparan Sulfate Proteoglycans
  • RNA, Messenger
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • perlecan
  • Vascular Endothelial Growth Factor Receptor-2