Signals and genes induced by angiogenic growth factors in comparison to inflammatory cytokines in endothelial cells
Issue title: Selected Papers from 1st Meeting on “Cardiovascular Biology: Endothelial Cell in Health and Hypertension”, 30 June–1 July 2006, Prague, Czech Republic
Affiliations: Department of Vascular Biology and Thrombosis Research, Center for Biomolecular Medicine and Pharmacology, Medical University of Vienna, Vienna, Austria
Note: [] Present address: Jiří Pomyje, MD, PhD, IVAX Pharmaceuticals Ltd., Anděl City, Radlická 1c, 150 00 Praha 5, Czech Republic.
Note: [] Corresponding author: Dr. Erhard Hofer, Department of Vascular Biology and Thrombosis Research, Center for Biomolecular Medicine and Pharmacology, Medical University of Vienna, Lazarettgasse 19, A-1090 Vienna, Austria. Tel.: +43 1 40160 33111; Fax: +43 1 40160 339100; E-mail: erhard.hofer@meduniwien.ac.at
Abstract: The evaluation of signaling pathways leading to gene induction by VEGF-A and IL-1 in endothelial cells supports the importance of the NF-κB pathway for the IL-1-induced gene repertoire, whereas VEGF-A is a strong and preferential trigger of signals via PLC-γ. This leads (i) via Ca++ to the activation of calcineurin and NFAT and (ii) via PKC and the MEK/ERK MAPK pathway to the upregulation of EGR-1. Part of the VEGF-triggered gene induction depends on a cooperation of the transcription factors NFAT and EGR-1. Gene activation via PLC-γ provides VEGF with the potency to induce a wide spectrum of genes including many also upregulated by IL-1. A gene upregulated by VEGF and IL-1 is the DSCR-1 gene, which encodes an inhibitor of calcineurin. DSCR1 is induced by NFAT or NF-κB and limits Ca++ signaling in a negative feed-back loop. Similarly, NAB2, a corepressor of EGR-1, is induced by EGR-1 and limits EGR-1 effects. Adenoviral overexpression of DSCR1 or NAB2 inhibited part of VEGF-induced gene expression and reduced sprouting in angiogenesis models.
