Article (Scientific journals)
Synergism between vascular endothelial growth factor and placental growth factor contributes to angiogenesis and plasma extravasation in pathological conditions
Carmeliet, Peter; Moons, Lieve; Luttun, Aernout et al.
2001In Nature Medicine, 7 (5), p. 575-583
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Abstract :
[en] 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.
Disciplines :
Anatomy (cytology, histology, embryology...) & physiology
Author, co-author :
Carmeliet, Peter
Moons, Lieve
Luttun, Aernout
Vincenti
Compernolle, Veerle
De mol, Maria
Wu, Yan
Bono, Françoise
Devy, Laetitia
Beck, Heike
Scholz, Dimitri
Acker, Till
Dipalma, Tina
Dewerchin, Mieke
Noël, Agnès ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie cellulaire et moléculaire appliquée à l'homme
Stalmans, Ingeborg
Barra, Adriano
Blacher, Silvia ;  Université de Liège - ULiège > Département des sciences cliniques > Labo de biologie des tumeurs et du développement
Vandendriessche, Thierry
Ponten, Anica
Eriksson, Ulf
Plate, Karl H
Foidart, Jean-Michel ;  Université de Liège - ULiège > Département des sciences cliniques > Gynécologie - Obstétrique - Labo de biologie des tumeurs et du développement
Schaper
Charnock-Jones, Stephen
Hicklin, Daniel
Herbert, Jean-Marc
Collen, Désiré
Persico, Graziella
More authors (19 more) Less
Language :
English
Title :
Synergism between vascular endothelial growth factor and placental growth factor contributes to angiogenesis and plasma extravasation in pathological conditions
Publication date :
2001
Journal title :
Nature Medicine
ISSN :
1078-8956
eISSN :
1546-170X
Publisher :
Nature Publishing Group, New York, United States - New York
Volume :
7
Issue :
5
Pages :
575-583
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 15 July 2009

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