Synergism between vascular endothelial growth factor and placental growth factor contributes to angiogenesis and plasma extravasation in pathological conditions

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...

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Published in:	Nature medicine Vol. 7; no. 5; pp. 575 - 583
Main Authors:	Carmeliet, Peter, Moons, Lieve, Luttun, Aernout, Vincenti, Valeria, Compernolle, Veerle, De Mol, Maria, Wu, Yan, Bono, Françoise, Devy, Laetitia, Beck, Heike, Scholz, Dimitri, Acker, Till, DiPalma, Tina, Dewerchin, Mieke, Noel, Agnes, Stalmans, Ingeborg, Barra, Adriano, Blacher, Sylvia, Vandendriessche, Thierry, Ponten, Annica, Eriksson, Ulf, Plate, Karl H, Foidart, Jean-Michel, Schaper, Wolfgang, Charnock-Jones, D. Stephen, Hicklin, Daniel J, Herbert, Jean-Marc, Collen, Désiré, Persico, M. Graziella
Format:	Journal Article Web Resource
Language:	English
Published:	United States Nature Publishing Group 01-05-2001
Subjects:	Anatomie (cytologie, histologie, embryologie...) & physiologie Anatomy (cytology, histology, embryology...) & physiology Angiogenesis Animals Base Sequence Basic Medicine Bone marrow Cancer Capillary Permeability Cell and Molecular Biology Cell- och molekylärbiologi DNA Primers Embryonic and Fetal Development Endothelial Growth Factors - physiology Fibrosarcoma Histamine Ischemia Kinases Life sciences Ligands Lymphokines - physiology Medical and Health Sciences Medical research Medicin och hälsovetenskap Medicinska och farmaceutiska grundvetenskaper Mice Neoplasms, Experimental - blood supply Neovascularization, Pathologic Permeability Placenta Growth Factor Plasma Pregnancy Proteins - genetics Pregnancy Proteins - physiology Publishing Reverse Transcriptase Polymerase Chain Reaction Sciences du vivant Synergism Tumors Vascular endothelial growth factor Vascular Endothelial Growth Factor A Vascular Endothelial Growth Factors Wound Healing - physiology Belgium New York United States > US
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 scopus-id:2-s2.0-19244379078
ISSN:	1078-8956 1546-170X 1546-170X
DOI:	10.1038/87904