title: Revascularization of ischemic tissues by PlGF treatment, and inhibition of tumor angiogenesis, arthritis and atherosclerosis by anti-Flt1.
abstract: 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.
authors.affiliation: Center for Transgene Technology and Gene Therapy, Flanders Interuniversity Institute for Biotechnology, University of Leuven, Leuven, Belgium.
authors.forename: Aernout
authors.initials: A
authors.lastname: Luttun
authors.forename: Marc
authors.initials: M
authors.lastname: Tjwa
authors.forename: Lieve
authors.initials: L
authors.lastname: Moons
authors.forename: Yan
authors.initials: Y
authors.lastname: Wu
authors.forename: Anne
authors.initials: A
authors.lastname: Angelillo-Scherrer
authors.forename: Fang
authors.initials: F
authors.lastname: Liao
authors.forename: Janice A
authors.initials: JA
authors.lastname: Nagy
authors.forename: Andrea
authors.initials: A
authors.lastname: Hooper
authors.forename: Josef
authors.initials: J
authors.lastname: Priller
authors.forename: Bert
authors.initials: B
authors.lastname: De Klerck
authors.forename: Veerle
authors.initials: V
authors.lastname: Compernolle
authors.forename: Evis
authors.initials: E
authors.lastname: Daci
authors.forename: Peter
authors.initials: P
authors.lastname: Bohlen
authors.forename: Mieke
authors.initials: M
authors.lastname: Dewerchin
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Herbert
authors.forename: Roy
authors.initials: R
authors.lastname: Fava
authors.forename: Patrick
authors.initials: P
authors.lastname: Matthys
authors.forename: Geert
authors.initials: G
authors.lastname: Carmeliet
authors.forename: Désiré
authors.initials: D
authors.lastname: Collen
authors.forename: Harold F
authors.initials: HF
authors.lastname: Dvorak
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Hicklin
authors.forename: Peter
authors.initials: P
authors.lastname: Carmeliet
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use*; D001161:Arteriosclerosis / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000473:pathology; D001808:Blood Vessels / Q000166:cytology / Q000187:drug effects / Q000473:pathology; D004195:Disease Models, Animal; D016228:Endothelial Growth Factors / Q000494:pharmacology; D005260:Female; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D006614:Hindlimb / Q000098:blood supply; D006801:Humans; D007511:Ischemia / Q000188:drug therapy / Q000473:pathology; D007596:Joints / Q000473:pathology; D008222:Lymphokines / Q000494:pharmacology; D051379:Mice; D008819:Mice, Nude; D017202:Myocardial Ischemia / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D018919:Neovascularization, Physiologic / Q000187:drug effects; D000072483:Placenta Growth Factor; D011257:Pregnancy Proteins / Q000235:genetics / Q000494:pharmacology* / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000276:immunology* / Q000378:metabolism; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000276:immunology* / Q000378:metabolism; D017978:Receptors, Growth Factor / Q000276:immunology / Q000378:metabolism; D040262:Receptors, Vascular Endothelial Growth Factor; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1; D042442:Vascular Endothelial Growth Factors
chemical_list: D000911:Antibodies, Monoclonal; D016228:Endothelial Growth Factors; D008222:Lymphokines; C000608036:PGF protein, human; C000608037:Pgf protein, mouse; C000608038:Pgf protein, rat; D011257:Pregnancy Proteins; D011518:Proto-Oncogene Proteins; D017978:Receptors, Growth Factor; D011993:Recombinant Fusion Proteins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D000072483:Placenta Growth Factor; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor; D040281:Vascular Endothelial Growth Factor Receptor-1