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p38 MAP Kinase—a molecular switch between VEGF‐induced angiogenesis and vascular hyperpermeability
Author(s) -
Issbrücker Katja,
Martin Hugo H.,
Hippenstiel Stefan,
Springmann Georg,
Voswinckel Robert,
Gaumann Andreas,
Breier Georg,
Drexler Hannes C. A.,
Suttorp Norbert,
Clauss Matthias
Publication year - 2003
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.02-0329fje
Subject(s) - angiogenesis , vascular endothelial growth factor , mapk/erk pathway , vascular permeability , vasculogenesis , p38 mitogen activated protein kinases , vascular endothelial growth factor a , in vivo , microbiology and biotechnology , cancer research , neovascularization , kinase , chemistry , in vitro , medicine , endothelial stem cell , biology , pathology , vegf receptors , biochemistry
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.