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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Antibodies, Monoclonal / pharmacology
-
Antibodies, Monoclonal / therapeutic use*
-
Arteriosclerosis / drug therapy*
-
Arteriosclerosis / immunology
-
Arteriosclerosis / pathology
-
Arthritis, Experimental / drug therapy*
-
Arthritis, Experimental / pathology
-
Blood Vessels / cytology
-
Blood Vessels / drug effects
-
Blood Vessels / pathology
-
Disease Models, Animal
-
Endothelial Growth Factors / pharmacology
-
Female
-
Hematopoietic Stem Cells / drug effects
-
Hindlimb / blood supply
-
Humans
-
Ischemia / drug therapy
-
Ischemia / pathology
-
Joints / pathology
-
Lymphokines / pharmacology
-
Mice
-
Mice, Nude
-
Myocardial Ischemia / drug therapy
-
Myocardial Ischemia / pathology
-
Myocardial Ischemia / physiopathology
-
Neovascularization, Pathologic / drug therapy*
-
Neovascularization, Physiologic* / drug effects
-
Placenta Growth Factor
-
Pregnancy Proteins / genetics
-
Pregnancy Proteins / pharmacology*
-
Pregnancy Proteins / physiology
-
Proto-Oncogene Proteins / immunology*
-
Proto-Oncogene Proteins / metabolism
-
Rats
-
Receptor Protein-Tyrosine Kinases / immunology*
-
Receptor Protein-Tyrosine Kinases / metabolism
-
Receptors, Growth Factor / immunology
-
Receptors, Growth Factor / metabolism
-
Receptors, Vascular Endothelial Growth Factor
-
Recombinant Fusion Proteins / genetics
-
Recombinant Fusion Proteins / metabolism
-
Vascular Endothelial Growth Factor A
-
Vascular Endothelial Growth Factor Receptor-1
-
Vascular Endothelial Growth Factors
Substances
-
Antibodies, Monoclonal
-
Endothelial Growth Factors
-
Lymphokines
-
PGF protein, human
-
Pgf protein, mouse
-
Pgf protein, rat
-
Pregnancy Proteins
-
Proto-Oncogene Proteins
-
Receptors, Growth Factor
-
Recombinant Fusion Proteins
-
Vascular Endothelial Growth Factor A
-
Vascular Endothelial Growth Factors
-
Placenta Growth Factor
-
Receptor Protein-Tyrosine Kinases
-
Receptors, Vascular Endothelial Growth Factor
-
Vascular Endothelial Growth Factor Receptor-1