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