Hypoxia induces permeability in brain microvessel endothelial cells via VEGF and NO

Silvia Fischer, Matthias Clauss, Marion Wiesnet, Dieter Renz, Wolfgang Schafer, Gerhard F. Karliczek

Research output: Contribution to journalArticle

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Abstract

In this study, an in vitro model of the blood-brain barrier, consisting of porcine brain-derived microvascular endothelial cells (BMEC), was used to evaluate the mechanism of hypoxia-induced hyperpermeability. We show that hypoxia-induced permeability in BMEC was completely abolished by a neutralizing antibody to vascular endothelial growth factor (VEGF). In contrast, under normoxic conditions, addition of VEGF up to 100 ng/ml did not alter monolayer barrier function. Treatment with either hypoxia or VEGF under normoxic conditions induced a twofold increase in VEGF binding sites and VEGF receptor 1 (Flt-1) mRNA expression in BMEC. Hypoxia-induced permeability also was prevented by the nitric oxide (NO) synthase inhibitor N(G)-monomethyl-L- arginine, suggesting that NO is involved in hypoxia-induced permeability changes, which was confirmed by measurements of the cGMP level. During normoxia, treatment with VEGF (5 ng/ml) increased permeability as well as cGMP content in the presence of several antioxidants. These results suggest that hypoxia-induced permeability in vitro is mediated by the VEGF/VEGF receptor system in an autocrine manner and is essentially dependent on reducing conditions stabilizing the second messenger NO as the mediator of changes in barrier function of BMEC.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Cell Physiology
Volume276
Issue number4 45-4
StatePublished - 1999
Externally publishedYes

Fingerprint

Endothelial cells
Microvessels
Vascular Endothelial Growth Factor A
Permeability
Brain
Nitric Oxide
Endothelial Cells
Vascular Endothelial Growth Factor Receptor-1
Vascular Endothelial Growth Factor Receptor
Second Messenger Systems
Neutralizing Antibodies
Blood-Brain Barrier
Nitric Oxide Synthase
Arginine
Hypoxia
Monolayers
Swine
Antioxidants
Binding Sites
Messenger RNA

Keywords

  • Blood-brain barrier
  • Endothelial barrier function
  • Hyperpermeability
  • Nitric oxide
  • Vascular endothelial growth factor

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology
  • Physiology (medical)

Cite this

Hypoxia induces permeability in brain microvessel endothelial cells via VEGF and NO. / Fischer, Silvia; Clauss, Matthias; Wiesnet, Marion; Renz, Dieter; Schafer, Wolfgang; Karliczek, Gerhard F.

In: American Journal of Physiology - Cell Physiology, Vol. 276, No. 4 45-4, 1999.

Research output: Contribution to journalArticle

Fischer, Silvia ; Clauss, Matthias ; Wiesnet, Marion ; Renz, Dieter ; Schafer, Wolfgang ; Karliczek, Gerhard F. / Hypoxia induces permeability in brain microvessel endothelial cells via VEGF and NO. In: American Journal of Physiology - Cell Physiology. 1999 ; Vol. 276, No. 4 45-4.
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