Revascularization of ischemic tissues by PlGF treatment,and inhibition of tumor angiogenesis,arthritis and atherosclerosis by anti-Flt1 |
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Authors: | Luttun Aernout Tjwa Marc Moons Lieve Wu Yan Angelillo-Scherrer Anne Liao Fang Nagy Janice A Hooper Andrea Priller Josef De Klerck Bert Compernolle Veerle Daci Evis Bohlen Peter Dewerchin Mieke Herbert Jean-Marc Fava Roy Matthys Patrick Carmeliet Geert Collen Désiré Dvorak Harold F Hicklin Daniel J Carmeliet Peter |
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Institution: | Center for Transgene Technology and Gene Therapy, Flanders Interuniversity Institute for Biotechnology, University of Leuven, Leuven, Belgium. |
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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. |
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