Back to Search
Start Over
Synergism between vascular endothelial growth factor and placental growth factor contributes to angiogenesis and plasma extravasation in pathological conditions
- Source :
- Nature Medicine. May, 2001, Vol. 7 Issue 5, p575, 9 p.
- Publication Year :
- 2001
-
Abstract
- 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[sup.-/-]). VEGF-B, another ligand of VEGFR-1, did not rescue development in Pgf[sup.-/-] 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[sup.-/-] 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 &apos;angiogenic switch&apos; in many pathological disorders.<br />Author(s): Peter Carmeliet (corresponding author) [1]; Lieve Moons [1]; Aernout Luttun [1]; Valeria Vincenti [2]; Veerle Compernolle [1]; Maria De Mol [1]; Yan Wu [3]; Francoise Bono [4]; Laetitia Devy [...]
Details
- Language :
- English
- ISSN :
- 10788956
- Volume :
- 7
- Issue :
- 5
- Database :
- Gale General OneFile
- Journal :
- Nature Medicine
- Publication Type :
- Academic Journal
- Accession number :
- edsgcl.193842026
- Full Text :
- https://doi.org/10.1038/87904