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

Citation
P. Carmeliet et al., Synergism between vascular endothelial growth factor and placental growth factor contributes to angiogenesis and plasma extravasation in pathologicalconditions, NAT MED, 7(5), 2001, pp. 575-583
Citations number
45
Categorie Soggetti
Research/Laboratory Medicine & Medical Tecnology","Medical Research General Topics
Journal title
NATURE MEDICINE
ISSN journal
10788956 → ACNP
Volume
7
Issue
5
Year of publication
2001
Pages
575 - 583
Database
ISI
SICI code
1078-8956(200105)7:5<575:SBVEGF>2.0.ZU;2-N
Abstract
Vascular endothelial growth factor (VEGF) stimulates angiogenesis by activa ting VEGF receptor-2 (VEGFR-2). The role of its homolog, placental growth f actor (PIGF), remains unknown. Both VEGF and PIGF bind to VEGF receptor-1 ( VEGFR-1), but it is unknown whether VECFR-1, which exists as a soluble or a membrane-bound type, is an inert decoy or a signaling receptor for PIGF du ring angiogenesis. Here, we report that embryonic angiogenesis in mice was not affected by deficiency of PIGF (Pgf(-/-)). VEGF-B, another ligand of VE GFR-1, did not rescue development in Pgf(-/-) mice. However, loss of PIGF i mpaired angiogenesis, plasma extravasation and collateral growth during isc hemia, inflammation, wound healing and cancer. Transplantation of wild-type bone marrow rescued the impaired angiogenesis and collateral growth in Pgf (-/-) mice, indicating that PIGF might have contributed to vessel growth in the adult by mobilizing bone-marrow-derived cells. The synergism between P IGF and VEGF was specific, as PIGF deficiency impaired the response to VEGF , but not to bFGF or histamine. VECFR-1 was activated by PIGF, given that a nti-VEGFR-1 antibodies and a Src-kinase inhibitor blocked the endothelial r esponse to PIGF or VEGF/PIGF. By upregulating PIGF and the signaling subtyp e of VEGFR-1, endothelial cells amplify their responsiveness to VEGF during the 'angiogenic switch' in many pathological disorders.