p38 MAP kinase--a molecular switch between VEGF-induced angiogenesis and vascular hyperpermeability.

Katja Issbrücker, Hugo H. Marti, Stefan Hippenstiel, Georg Springmann, Robert Voswinckel, Andreas Gaumann, Georg Breier, Hannes C.A. Drexler, Norbert Suttorp, Matthias Clauss

Research output: Contribution to journalArticle

139 Scopus citations

Abstract

Vascular endothelial growth factor (VEGF) is not only essential for vasculogenesis and angiogenesis but also is a potent inducer of vascular permeability. Although a dissection of the molecular pathways between angiogenesis- and vascular permeability-inducing properties would be desirable for the development of angiogenic and anti-angiogenic therapies, such mechanisms have not been identified yet. Here we provide evidence for a role of the p38 MAPK as the signaling molecule that separates these two processes. Inhibition of p38 MAPK activity enhances VEGF-induced angiogenesis in vitro and in vivo, a finding that was accompanied by prolonged Erk1/2 MAPK activation, increased endothelial survival, and plasminogen activation. Conversely, the same inhibitors abrogate VEGF-induced vascular permeability in vitro and in vivo. These dualistic properties of p38 MAPK are relevant not only for therapeutic angiogenesis but also for reducing edema formation and enhancing tissue repair in ischemic diseases.

Original languageEnglish (US)
Pages (from-to)262-264
Number of pages3
JournalThe FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Volume17
Issue number2
StatePublished - Feb 2003
Externally publishedYes

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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    Issbrücker, K., Marti, H. H., Hippenstiel, S., Springmann, G., Voswinckel, R., Gaumann, A., Breier, G., Drexler, H. C. A., Suttorp, N., & Clauss, M. (2003). p38 MAP kinase--a molecular switch between VEGF-induced angiogenesis and vascular hyperpermeability. The FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 17(2), 262-264.