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Akt signaling mediates VEGF/VPF vascular permeability in vivo
Author(s) -
Six Isabelle,
Kureishi Yasuko,
Luo Zhengyu,
Walsh Kenneth
Publication year - 2002
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(02)03630-x
Subject(s) - protein kinase b , vascular permeability , microbiology and biotechnology , pi3k/akt/mtor pathway , angiogenesis , signal transduction , vascular endothelial growth factor a , chemistry , vascular endothelial growth factor , cancer research , biology , endocrinology , vegf receptors
VEGF is an endothelial cell cytokine that promotes angiogenesis and enhances microvascular permeability. Recently, it has been shown that the protein kinase Akt functions in a key intercellular signaling pathway downstream of VEGF. Here, we employed adenovirus‐mediated gene transfer in conjunction with the Miles assay in hairless albino guinea pigs to assess the role of Akt signaling in vascular permeability. VEGF‐induced vascular permeability was blocked by the transduction of a dominant negative mutant of Akt. Conversely, transduction of a constitutively active form of Akt promoted vascular permeability in a manner similar to VEGF protein administration. This Akt‐mediated increase in vascular permeability was inhibited by the eNOS inhibitor L‐NAME. These data show that Akt signaling is both necessary and sufficient for vascular permeability in an in vivo model.