Meny

Javascript verkar inte påslaget? - Vissa delar av Lunds universitets webbplats fungerar inte optimalt utan javascript, kontrollera din webbläsares inställningar.
Du är här

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

Författare:
  • Peter Carmeliet
  • Lieve Moons
  • Aernout Luttun
  • Valeria Vincenti
  • Veerle Compernolle
  • Maria De Mol
  • Yan Wu
  • Françoise Bono
  • Laetitia Devy
  • Heike Beck
  • Dimitri Scholz
  • Till Acker
  • Tina DiPalma
  • Mieke Dewerchin
  • Agnes Noel
  • Ingeborg Stalmans
  • Adriano Barra
  • Sylvia Blacher
  • Thierry Vandendriessche
  • Annica Pontén
  • Ulf Eriksson
  • Karl H. Plate
  • Jean-Michel Foidart
  • Wolfgang Schaper
  • D. Stephen Charnock-Jones
  • Daniel J. Hicklin
  • Jean-Marc Herbert
  • Désiré Collen
  • M. Graziella Persico
Publiceringsår: 2001
Språk: Engelska
Sidor: 575-583
Publikation/Tidskrift/Serie: Nature medicine
Volym: 7
Nummer: 5
Dokumenttyp: Artikel
Förlag: Nature Publishing Group

Sammanfattning

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.

Disputation

Nyckelord

  • Medicine and Health Sciences

Övriga

Published
Yes
  • ISSN: 1078-8956

Box 117, 221 00 LUND
Telefon 046-222 00 00 (växel)
Telefax 046-222 47 20
lu [at] lu [dot] se

Fakturaadress: Box 188, 221 00 LUND
Organisationsnummer: 202100-3211
Om webbplatsen