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Schweighofer, B; Testori, J; Sturtzel, C; Sattler, S; Mayer, H; Wagner, O; Bilban, M; Hofer, E.
The VEGF-induced transcriptional response comprises gene clusters at the crossroad of angiogenesis and inflammation.
Thromb Haemost. 2009; 102(3): 544-54.
Doi: 10.1160/TH08-12-0830
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- Co-Autor*innen der Med Uni Graz
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Sattler Susanne
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- Abstract:
- VEGF-A is the major trigger of vasculogenesis and physiologic angiogenesis. We have investigated to which extent the gene repertoire induced by VEGF-A in endothelial cells is distinct from that of other growth factors and inflammatory cytokines. Genes upregulated in human umbilical vein endothelial cells treated with VEGF, EGF or IL-1 were compared by microarray analysis and clusters characteristic for individual or combinations of inducers were defined. VEGF-A upregulated in comparison to EGF a five-fold larger gene repertoire, which surprisingly overlapped to 60% with the inflammatory repertoire of IL-1. As shown by real-time RT-PCR for selected genes, VEGF-induction was mostly mediated by VEGF receptor-2 and the capacity of VEGF-A to induce genes in common with IL-1 largely depended on activation of the calcineurin/NFAT pathway, since cyclosporin A inhibited this induction. Another angiogenic growth factor, bFGF, did not share a comparable induction of inflammatory genes, but partially induced a small group of genes in common with VEGF-A, which were not regulated by EGF. Thus, the data display that VEGF-A induces a distinct gene repertoire, which, contrasting with other growth factors such as EGF or bFGF, includes an inherent inflammatory component possibly contributing to the cross-regulation of angiogenesis and inflammation as further indicated by the VEGF-mediated induction of leukocyte adhesion. Furthermore, a small group of genes selectively induced by VEGF-A with potential importance for angiogenesis is defined.
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Calcineurin - metabolism
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Cyclosporine - metabolism
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Endothelial Cells - cytology
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Gene Expression Regulation - administration & dosage
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Humans - administration & dosage
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Inflammation - administration & dosage
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Interleukin-1 - metabolism
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Models, Genetic - administration & dosage
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Multigene Family - administration & dosage
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Neovascularization, Pathologic - administration & dosage
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Oligonucleotide Array Sequence Analysis - administration & dosage
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Reverse Transcriptase Polymerase Chain Reaction - administration & dosage
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Transcription, Genetic - administration & dosage
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Vascular Endothelial Growth Factor A - metabolism
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Vascular Endothelial Growth Factor Receptor-2 - metabolism
- Find related publications in this database (Keywords)
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VEGF-A
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endothelial cells
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angiogenesis
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inflammation
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gene repertoire