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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 [OPEN ACCESS]
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Co-Autor*innen der Med Uni Graz
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.
Find related publications in this database (using NLM MeSH Indexing)
Calcineurin - metabolism
Cyclosporine - metabolism
Endothelial Cells - cytology
Gene Expression Regulation - administration & dosage
Humans - administration & dosage
Inflammation - administration & dosage
Interleukin-1 - metabolism
Models, Genetic - administration & dosage
Multigene Family - administration & dosage
Neovascularization, Pathologic - administration & dosage
Oligonucleotide Array Sequence Analysis - administration & dosage
Reverse Transcriptase Polymerase Chain Reaction - administration & dosage
Transcription, Genetic - administration & dosage
Vascular Endothelial Growth Factor A - metabolism
Vascular Endothelial Growth Factor Receptor-2 - metabolism

Find related publications in this database (Keywords)
VEGF-A
endothelial cells
angiogenesis
inflammation
gene repertoire
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