Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-2951
Andrés, G; Leali, D; Mitola, S; Coltrini, D; Camozzi, M; Corsini, M; Belleri, M; Hirsch, E; Schwendener, R; Christofori, G; Alcamí, A; Presta, M (2009). A pro-inflammatory signature mediates FGF2-induced angiogenesis. Journal of Cellular and Molecular Medicine, 13(8b):2083-2108.
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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 evidenced a significant monocyte/macrophage infiltrate in the areas of FGF2-driven neovascularization. Similar results were obtained when the conditioned medium 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 leukocyte 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 conditioned medium 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 nonredundant role for inflammatory cells in the neovascularization process elicited by the growth factor.
|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||04 Faculty of Medicine > Institute of Molecular Cancer Research|
07 Faculty of Science > Institute of Molecular Cancer Research
|DDC:||570 Life sciences; biology|
|Date:||09 August 2009|
|Deposited On:||29 Aug 2008 17:14|
|Last Modified:||23 Nov 2012 14:18|
|Additional Information:||Author Posting. © The Authors 2008. This is the author's version of the work. It is posted here for personal use, not for redistribution. The definitive version was published in J. Cell. Mol. Med. Vol 13, No 8B, 2009 pp. 2083-2108, http://dx.doi.org/10.1111/j.1582-4934.2008.00415.x.|
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