Open AccessA pro‐inflammatory signature mediates FGF2‐induced angiogenesis
Author(s) -
Andrés Germán,
Leali Daria,
Mitola Stefania,
Coltrini Daniela,
Camozzi Maura,
Corsini Michela,
Belleri Mirella,
Hirsch Emilio,
Schwendener Reto A.,
Christofori Gerhard,
Alcamì Antonio,
Presta Marco
Publication year - 2009
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/j.1582-4934.2008.00415.x
Subject(s) - angiogenesis , fibroblast growth factor , neovascularization , chemokine , microbiology and biotechnology , matrigel , angiopoietin , inflammation , s1pr1 , immunology , biology , vascular endothelial growth factor , cxc chemokine receptors , cxcl1 , endothelial stem cell , cancer research , cytokine , vascular endothelial growth factor a , chemokine receptor , receptor , in vitro , biochemistry , vegf receptors
Abstract Fibroblast growth factor‐2 (FGF2) is a potent angiogenic growth factor. Here, gene expression profiling of FGF2‐stimulated microvascular endothelial cells revealed, together with a prominent pro‐angiogenic profile, a pro‐inflammatory signature characterized by the up‐regulation of pro‐inflammatory cytokine/chemokines and their receptors, endothelial cell adhesion molecules and members of the eicosanoid pathway. Real‐time quantitative PCR demonstrated early induction of most of the FGF2‐induced, inflammation‐related genes. Accordingly, chick embryo chorioallantoic membrane (CAM) and murine Matrigel plug angiogenesis assays demonstrated a significant monocyte/macrophage infiltrate in the areas of FGF2‐driven neovascularization. Similar results were obtained when the conditioned medium (CM) of FGF2‐stimulated endothelial cells was delivered onto the CAM, suggesting that FGF2‐upregulated chemoattractants mediate the inflammatory response. Importantly, FGF2‐triggered new blood vessel formation was significantly reduced in phosphatidylinositol 3‐kinase ‐γ null mice exhibiting defective leucocyte migration or in clodronate liposome‐treated, macrophage‐depleted mice. Furthermore, the viral pan‐chemokine antagonist M3 inhibited the angiogenic and inflammatory responses induced by the CM of FGF2‐stimulated endothelial cells and impaired FGF2‐driven neovascularization in the CAM assay. These findings point to inflammatory chemokines as early mediators of FGF2‐driven angiogenesis and indicate a non‐redundant role for inflammatory cells in the neovascularization process elicited by the growth factor.