VEGF induces hyperpermeability by a direct action on endothelial cells

S. Hippenstiel, M. Krüll, A. Ikemann, W. Risau, M. Clauss, Norbert Suttorp

Research output: Contribution to journalArticle

166 Scopus citations

Abstract

Vascular endothelial growth factor (VEGF) is a key regulator of vasculo- and angiogenesis. Earlier studies demonstrated a permeability-increasing effect of VEGF in skin tests, leading to its other name, vascular permeability factor. We wondered whether VEGF-induced hyperpermeability was a direct effect of VEGF on endothelial cells and studied the permeability of human and porcine endothelial cell monolayers in a well-characterized in vitro system. VEGF increased the hydraulic conductivity up to 20-fold and simultaneously decreased the albumin reflection coefficient. This effect occurred after a delay of 150 min, although VEGF-induced early endothelial cell activation was verified by enhanced inositol phosphate accumulation within 5 min and increased P-selectin expression within 15 min. Platelet- derived growth factor and granulocyte-macrophage colony-stimulating factor, two endothelial cell nonspecific mitogens, also stimulated phosphatidylinositol metabolism and P-selectin expression; however, they had no effect on endothelial permeability. The increase in intracellular cyclic nucleotide levels of human endothelial monolayers abolished VEGF-induced endothelial hyperpermeability. In summary, VEGF increased endothelial permeability by a direct action on endothelial cells. Based on the pattern of endothelial cell activation by growth factors, VEGF appears to be a unique stimulus.

Original languageEnglish (US)
Pages (from-to)L678-L684
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume274
Issue number5 18-5
DOIs
StatePublished - May 1998

Keywords

  • Adhesion molecules
  • Cultured human endothelial cells
  • Granulocyte-macrophage colony-stimulating factor
  • Hydraulic conductivity
  • Platelet-derived growth factor
  • Vascular endothelial growth factor

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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