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

• 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
• ISSN: 1078-8956; 1546-170X; 1546-170X
• DOI: 10.1038/87904

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.