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The anti‐angiogenic vascular endothelial growth factor isoform, VEGF165b transiently increases microvascular hydraulic conductivity independently of VEGF receptor 2 signalling in vivo
Author(s) -
Glass Catherine Ann,
Harper Steven,
Bates David Owen
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a705-d
Subject(s) - angiogenesis , in vivo , vascular endothelial growth factor , receptor , vascular permeability , medicine , endocrinology , chemistry , vegf receptors , biology , microbiology and biotechnology
VEGF 165 is a potent angiogenic factor that increases microvascular permeability by VEGF receptor 2 (VEGFR‐2) signalling (1). VEGF 165 b is an endogenous splice variant of VEGF (2) that inhibits VEGF 165 induced angiogenesis (3). We recently showed that VEGF 165 b transiently increases hydraulic conductivity (4). The aim of this study was to determine if VEGF 165 b also increases permeability through VEGFR‐2 signalling. Hydraulic conductivity, L p was measured in MS222 anaesthetized frogs using the Landis‐Michel micro‐occlusion method (5). All animals were humanely killed at the end of the procedure. 14 mesenteric microvessels were perfused with 1% BSA then perfused with 1nM VEGF 165 b. L p (x10 −7 cm.s −1 .cmH 2 O −1 ) increased 2.7 ± 0.4 fold (mean±sem) from 1.8 ± 0.4 with BSA to a peak of 4.4 ± 1.2 with VEGF 165 b (p<0.01, Wilcoxon). The vessels were washed with 1% BSA for 10 minutes then with the VEGFR‐2 inhibitor, 10nM ZM323881 for 10 minutes before being perfused with VEGF 165 b and ZM323881. L p increased 2.2 ± 0.3 fold from 1.4 ± 0.3 with ZM323881 alone to 2.6 ± 0.5 with VEGF 165 b and ZM323881 (p=0.0001, Wilcoxon). There was no significant difference between the VEGF 165 b induced fold increases in Lp with or without ZM323881 (p>0.05, Wilcoxon). These results show that VEGF 165 b, unlike VEGF, acutely increases Lp independently of VEGFR‐2 signalling. This work was funded by The Richard Bright VEGF Fund and The Luff Fund.