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Title: Synergism between vascular endothelial growth factor and placental growth factor contributes to angiogenesis and plasma extravasation in pathological conditions
Authors: Carmeliet, Peter ×
Moons, Lieve
Luttun, Aernout
Vincenti, V
Compernolle, Veerle
De Mol, M
Wu, Y
Bono, F
Devy, L
Beck, H
Scholz, D
Acker, T
DiPalma, T
Dewerchin, Mieke
Noel, A
Stalmans, Ingeborg
Barra, A
Blacher, S
Vandendriessche, Thierry
Ponten, A
Eriksson, U
Plate, K H
Foidart, J M
Schaper, W
Charnock-Jones, D S
Hicklin, D J
Herbert, J M
Collen, Desire
Persico, M G #
Issue Date: May-2001
Publisher: Nature america inc
Series Title: Nature medicine vol:7 issue:5 pages:575-583
Abstract: Vascular endothelial growth factor (VEGF) stimulates angiogenesis by activating VEGF receptor-2 (VEGFR-2). The role of its homolog, placental growth factor (PlGF), remains unknown. Both VEGF and PlGF bind to VEGF receptor-1 (VEGFR-1), but it is unknown whether VEGFR-1, which exists as a soluble or a membrane-bound type, is an inert decoy or a signaling receptor for PlGF during angiogenesis. Here, we report that embryonic angiogenesis in mice was not affected by deficiency of PlGF (Pgf-/-). VEGF-B, another ligand of VEGFR-1, did not rescue development in Pgf-/- mice. However, loss of PlGF impaired angiogenesis, plasma extravasation and collateral growth during ischemia, inflammation, wound healing and cancer. Transplantation of wild-type bone marrow rescued the impaired angiogenesis and collateral growth in Pgf-/- mice, indicating that PlGF might have contributed to vessel growth in the adult by mobilizing bone-marrow-derived cells. The synergism between PlGF and VEGF was specific, as PlGF deficiency impaired the response to VEGF, but not to bFGF or histamine. VEGFR-1 was activated by PlGF, given that anti-VEGFR-1 antibodies and a Src-kinase inhibitor blocked the endothelial response to PlGF or VEGF/PlGF. By upregulating PlGF and the signaling subtype of VEGFR-1, endothelial cells amplify their responsiveness to VEGF during the 'angiogenic switch' in many pathological disorders.
URI: 
ISSN: 1078-8956
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Molecular and Vascular Biology
Research Group Ophthalmology
Animal Physiology and Neurobiology Section - miscellaneous
Laboratory of Angiogenesis and Vascular Metabolism (Vesalius Research Center) (+)
× corresponding author
# (joint) last author

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