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Title: Differential effect of various VEGF isoforms on endothelial cells and Tenon fibroblasts
Authors: Van Bergen, Tine ×
Vandewalle, Evelien
Van de Veire, Sara
Moons, Lieve
Stalmans, Ingeborg #
Issue Date: Nov-2011
Publisher: Academia Opthalmologica Belgica
Host Document: Bulletin de la Société belge d'ophtalmologie vol:317
Conference: OB Congress 2011 location:Brussels, Belgium date:23-25 November 2011
Abstract: PURPOSE To clarify the differential effects elicited by VEGF isoforms in scar
formation after glaucoma surgery, we compared the biological responses
and signaling pathways activated by the various isoforms on endothelial
cells (HUVEC) and Tenon fibroblasts (TF) in vitro.
METHODS VEGF-R2 and neuropilin-1 (NRP-1) expression was analyzed on
HUVEC and TF by RT-PCR. The effect of different VEGF isoforms (VEGF189,
VEGF165 and VEGF121) on HUVEC and TF proliferation was determined by
WST-1 assay. The extracellular signal-regulated kinase (ERK) pathway was
evaluated by TransAM c-Myc assay.
RESULTS HUVEC showed a higher expression of VEGF-R2 and NRP-1
mRNA as compared to TF. VEGF189 only significantly increased the growth
of TF, whereas VEGF165 only significantly increased HUVEC proliferation.
VEGF165 strongly binds VEGF-R2 and NRP-1. As such, the combined
reduced expression of VEGF-R2 and NRP-1 on TF explained why VEGF165
was more potent in inducing proliferation of HUVEC as compared to TF.
VEGF121 exerted significant proliferative effects on both cell types by
binding VEGF-R2. However, similar concentrations of VEGF121 stimulated
HUVEC more than TF, due to the lower expression of VEGF-R2 on TF. All
these stimulating effects on proliferation were associated with an activation
of the ERK pathway.
CONCLUSION Our data indicate that VEGF165 and VEGF121 predominantly
affect blood vessel growth, whereas VEGF189 may be more important in
fibrosis. Selective inhibition of VEGF165 (pegaptanib) may therefore be
less effective to reduce ocular scar formation than non-selective VEGFinhibition
(bevacizumab), presumably due to retained action of VEGF121
and VEGF189.
Publication status: published
KU Leuven publication type: AMa
Appears in Collections:Research Group Ophthalmology
Animal Physiology and Neurobiology Section - miscellaneous
× corresponding author
# (joint) last author

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