The anti-angiogenic VEGF isoform VEGF165b transiently increases hydraulic conductivity, probably through VEGF receptor 1 in vivo

• Published in: The Journal of physiology Vol. 572; no. 1; pp. 243 - 257
• Main Authors: Glass, C. A., Harper, S. J., Bates, D. O.
• Format: Journal Article
• Language: English
• Published: 9600 Garsington Road , Oxford , OX4 2DQ , UK The Physiological Society 01-04-2006; Blackwell Publishing Ltd; Blackwell Science Inc
• Subjects: Angiogenesis Inhibitors - administration & dosage; Animals; Capillary Permeability - drug effects; Capillary Permeability - physiology; Cardiovascular; Dose-Response Relationship, Drug; Kinetics; Male; Mesentery - blood supply; Mesentery - drug effects; Mesentery - physiology; Neovascularization, Physiologic - drug effects; Neovascularization, Physiologic - physiology; Protein Isoforms - administration & dosage; Ranidae; Rats; Rats, Wistar; Vascular Endothelial Growth Factor A - administration & dosage; Vascular Endothelial Growth Factor Receptor-1 - metabolism
• ISSN: 0022-3751; 1469-7793
• DOI: 10.1113/jphysiol.2005.103127

Vascular endothelial growth factor (VEGF) is the principal agent that increases microvascular permeability during physiological
and pathological angiogenesis. VEGF is differentially spliced to form two families of isoforms: VEGF xxx , and VEGF xxx b. Whereas VEGF 165 stimulates angiogenesis, VEGF 165 b is anti-angiogenic. To determine the effect of VEGF 165 b on permeability, hydraulic conductivity ( L p ) was measured in individually perfused microvessels in the mesentery of frogs and rats. As with VEGF 165 , VEGF 165 b increased L p in amphibian (2.4 ± 0.3-fold) and mammalian (1.9 ± 0.2-fold) mesenteric microvessels. A dose–response relationship showed
that VEGF 165 b (EC 50 , 0.65 p m ) was approximately 25 times more potent than VEGF 165 (EC 50 , 16 p m ) in amphibian microvessels. VEGF 165 has been shown to increase permeability through VEGF receptor 2 (VEGF-R2) signalling. However, VEGF 165 b increased L p of frog vessels to the same extent in the presence of the VEGF-R2 inhibitor ZM323881, indicating that it does not increase
permeability via VEGF-R2 signalling, and was inhibited by the VEGF receptor inhibitor SU5416 at doses that are specific for
VEGF receptor 1 (VEGF-R1). VEGF 165 b, in contrast to VEGF 165 , did not result in a sustained chronic increase in L p . These results show that although VEGF 165 b is anti-angiogenic in the mesentery, it does signal in endothelial cells in vivo resulting in a transient, but not sustained, increase in microvascular L p , probably through VEGF-R1.