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

Carmeliet, Peter ; Moons, Lieve ; Luttun, Aernout ; Vincenti, Valeria ; Compernolle, Veerle ; De Mol, Maria ; Wu, Yan ; Bono, Françoise ; Devy, Laetitia and Beck, Heike , et al. (2001) In Nature Medicine 7(5). p.575-583
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-/-). 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... (More)
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. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Nature Medicine
volume
7
issue
5
pages
575 - 583
publisher
Nature Publishing Group
external identifiers
  • pmid:11329059
  • scopus:19244379078
ISSN
1546-170X
DOI
10.1038/87904
language
English
LU publication?
yes
additional info
The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Hematopoietic Stem Cell Laboratory (013022012)
id
18665b1e-53c1-4d52-9c09-51299501c7f3 (old id 1121192)
date added to LUP
2016-04-01 16:04:54
date last changed
2022-08-29 23:36:04
@article{18665b1e-53c1-4d52-9c09-51299501c7f3,
  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-/-). 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.}},
  author       = {{Carmeliet, Peter and Moons, Lieve and Luttun, Aernout and Vincenti, Valeria and Compernolle, Veerle and De Mol, Maria and Wu, Yan and Bono, Françoise and Devy, Laetitia and Beck, Heike and Scholz, Dimitri and Acker, Till and DiPalma, Tina and Dewerchin, Mieke and Noel, Agnes and Stalmans, Ingeborg and Barra, Adriano and Blacher, Sylvia and Vandendriessche, Thierry and Pontén, Annica and Eriksson, Ulf and Plate, Karl H. and Foidart, Jean-Michel and Schaper, Wolfgang and Charnock-Jones, D. Stephen and Hicklin, Daniel J. and Herbert, Jean-Marc and Collen, Désiré and Persico, M. Graziella}},
  issn         = {{1546-170X}},
  language     = {{eng}},
  number       = {{5}},
  pages        = {{575--583}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Medicine}},
  title        = {{Synergism between vascular endothelial growth factor and placental growth factor contributes to angiogenesis and plasma extravasation in pathological conditions}},
  url          = {{http://dx.doi.org/10.1038/87904}},
  doi          = {{10.1038/87904}},
  volume       = {{7}},
  year         = {{2001}},
}