p38 MAP Kinase—a molecular switch between VEGF‐induced angiogenesis and vascular hyperpermeability

Autor: Hugo H. Marti, Hannes C.A. Drexler, Norbert Suttorp, Robert Voswinckel, Georg Breier, Andreas Gaumann, Matthias Clauss, Stefan Hippenstiel, Katja Issbrücker, Georg Springmann
Rok vydání: 2002
Předmět:
Vascular Endothelial Growth Factor A
Endothelium
Cell Survival
Pyridines
Angiogenesis
Neovascularization
Physiologic
Vascular permeability
Chick Embryo
Endothelial Growth Factors
Biology
p38 Mitogen-Activated Protein Kinases
Biochemistry
Capillary Permeability
Neovascularization
chemistry.chemical_compound
Vasculogenesis
Genetics
medicine
Animals
Humans
Therapeutic angiogenesis
Allantoin
Enzyme Inhibitors
Phosphorylation
Molecular Biology
Mitogen-Activated Protein Kinase 1
Lymphokines
Mitogen-Activated Protein Kinase 3
Neovascularization
Pathologic
Vascular Endothelial Growth Factors
Imidazoles
Plasminogen
Chorion
Cell biology
Vascular endothelial growth factor
Vascular endothelial growth factor A
medicine.anatomical_structure
chemistry
Intercellular Signaling Peptides and Proteins
Fibroblast Growth Factor 2
Endothelium
Vascular
Mitogen-Activated Protein Kinases
medicine.symptom
Biotechnology
Zdroj: The FASEB Journal. 17:262-264
ISSN: 1530-6860
0892-6638
DOI: 10.1096/fj.02-0329fje
Popis: 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.
Databáze: OpenAIRE
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