A pro-inflammatory signature mediates FGF2-induced angiogenesis

Andrés, Germán and Leali, Daria and Mitola, Stefania and Coltrini, Daniela and Camozzi, Maura and Corsini, Michela and Belleri, Mirella and Hirsch, Emilio and Schwendener, Reto A. and Christofori, Gerhard and Alcamí, Antonio and Presta, Marco. (2009) A pro-inflammatory signature mediates FGF2-induced angiogenesis. Journal of cellular and molecular medicine : an international journal, Vol. 13. pp. 2083-2108.

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Official URL: http://edoc.unibas.ch/dok/A6005844

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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 upregulation 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-gamma 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.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Former Units at DBM > Tumor Biology (Christofori)
UniBasel Contributors:Christofori, Gerhard M.
Item Type:Article, refereed
Article Subtype:Research Article
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:01 Feb 2013 08:46
Deposited On:01 Feb 2013 08:41

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