Revascularization of ischemic tissues by PlGF treatment, and inhibition of tumor angiogenesis, arthritis and atherosclerosis by anti-Flt1

Aernout Luttun, Marc Tjwa, Lieve Moons, Yan Wu, Anne Angelillo-Scherrer, Fang Liao, Janice A Nagy, Andrea Hooper, Josef Priller, Bert De Klerck, Veerle Compernolle, Evis Daci, Peter Bohlen, Mieke Dewerchin, Jean-Marc Herbert, Roy Fava, Patrick Matthys, Geert Carmeliet, Désiré Collen, Harold F DvorakDaniel J Hicklin, Peter Carmeliet

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

The therapeutic potential of placental growth factor (PlGF) and its receptor Flt1 in angiogenesis is poorly understood. Here, we report that PlGF stimulated angiogenesis and collateral growth in ischemic heart and limb with at least a comparable efficiency to vascular endothelial growth factor (VEGF). An antibody against Flt1 suppressed neovascularization in tumors and ischemic retina, and angiogenesis and inflammatory joint destruction in autoimmune arthritis. Anti-Flt1 also reduced atherosclerotic plaque growth and vulnerability, but the atheroprotective effect was not attributable to reduced plaque neovascularization. Inhibition of VEGF receptor Flk1 did not affect arthritis or atherosclerosis, indicating that inhibition of Flk1-driven angiogenesis alone was not sufficient to halt disease progression. The anti-inflammatory effects of anti-Flt1 were attributable to reduced mobilization of bone marrow-derived myeloid progenitors into the peripheral blood; impaired infiltration of Flt1-expressing leukocytes in inflamed tissues; and defective activation of myeloid cells. Thus, PlGF and Flt1 constitute potential candidates for therapeutic modulation of angiogenesis and inflammation.

Original languageEnglish
Pages (from-to)831-40
Number of pages10
JournalNature Medicine
Volume8
Issue number8
DOIs
Publication statusPublished - Aug 2002

Keywords / Materials (for Non-textual outputs)

  • Animals
  • Antibodies, Monoclonal
  • Arteriosclerosis
  • Arthritis, Experimental
  • Blood Vessels
  • Disease Models, Animal
  • Endothelial Growth Factors
  • Female
  • Hematopoietic Stem Cells
  • Hindlimb
  • Humans
  • Ischemia
  • Joints
  • Lymphokines
  • Mice
  • Mice, Nude
  • Myocardial Ischemia
  • Neovascularization, Pathologic
  • Neovascularization, Physiologic
  • Placenta Growth Factor
  • Pregnancy Proteins
  • Proto-Oncogene Proteins
  • Rats
  • Receptor Protein-Tyrosine Kinases
  • Receptors, Growth Factor
  • Receptors, Vascular Endothelial Growth Factor
  • Recombinant Fusion Proteins
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factor Receptor-1
  • Vascular Endothelial Growth Factors
  • Journal Article
  • Research Support, Non-U.S. Gov't

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