The VEGF-induced transcriptional response comprises gene clusters at the crossroad of angiogenesis and inflammation

Thromb Haemost. 2009 Sep;102(3):544-54. doi: 10.1160/TH08-12-0830.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calcineurin / metabolism
  • Cyclosporine / metabolism
  • Endothelial Cells / cytology
  • Gene Expression Regulation*
  • Humans
  • Inflammation*
  • Interleukin-1 / metabolism
  • Models, Genetic
  • Multigene Family
  • Neovascularization, Pathologic*
  • Oligonucleotide Array Sequence Analysis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription, Genetic*
  • Vascular Endothelial Growth Factor A / metabolism*
  • Vascular Endothelial Growth Factor Receptor-2 / metabolism


  • Interleukin-1
  • Vascular Endothelial Growth Factor A
  • Cyclosporine
  • Vascular Endothelial Growth Factor Receptor-2
  • Calcineurin