Signals and genes induced by angiogenic growth factors in comparison to inflammatory cytokines in endothelial cells

Clin Hemorheol Microcirc. 2007;37(1-2):57-62.


The evaluation of signaling pathways leading to gene induction by VEGF-A and IL-1 in endothelial cells supports the importance of the NF-kappaB pathway for the IL-1-induced gene repertoire, whereas VEGF-A is a strong and preferential trigger of signals via PLC-gamma. 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-gamma 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-kappaB 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Angiogenic Proteins / physiology*
  • Cytokines / physiology*
  • Endothelium, Vascular / cytology*
  • Gene Expression Regulation*
  • Interleukin-1 / physiology
  • Signal Transduction*
  • Transcriptional Activation
  • Vascular Endothelial Growth Factor A / physiology


  • Angiogenic Proteins
  • Cytokines
  • Interleukin-1
  • Vascular Endothelial Growth Factor A