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VEGF induces hyperpermeability by a direct action on endothelial cells
S Hippenstiel1, M Krüll, A Ikemann
1Department of Internal Medicine, Justus-Liebig-University, Giessen, Germany.
The American Journal of Physiology
|June 5, 1998
Summary
Vascular endothelial growth factor (VEGF) directly increases blood vessel permeability in endothelial cells. This effect, though delayed, is unique to VEGF and not seen with other growth factors.
Area of Science:
- Endocrinology
- Cell Biology
- Physiology
Background:
- Vascular endothelial growth factor (VEGF) is known to regulate blood vessel formation.
- VEGF has been observed to increase vascular permeability in vivo.
- The direct cellular mechanisms underlying VEGF's effect on permeability were not fully understood.
Purpose of the Study:
- To investigate whether VEGF directly increases endothelial cell permeability.
- To characterize the time course and specificity of VEGF-induced hyperpermeability.
Main Methods:
- Utilized an in vitro system with human and porcine endothelial cell monolayers.
- Measured hydraulic conductivity and albumin reflection coefficient.
- Assessed endothelial cell activation markers like inositol phosphate accumulation and P-selectin expression.
- Investigated the role of cyclic nucleotides in modulating VEGF effects.
Main Results:
- VEGF significantly increased endothelial hydraulic conductivity (up to 20-fold) and decreased albumin reflection coefficient.
- VEGF-induced hyperpermeability showed a delayed onset (150 min) but was preceded by early endothelial cell activation.
- Other mitogens (PDGF, GM-CSF) activated cells but did not alter permeability.
- Increased intracellular cyclic nucleotide levels abrogated VEGF-induced hyperpermeability.
Conclusions:
- VEGF directly increases endothelial cell permeability.
- VEGF is a unique stimulus for endothelial hyperpermeability, distinct from other growth factors.
- The findings provide insights into the specific mechanisms of VEGF action on vascular function.