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FEBS Lett. 2002 Dec 4;532(1-2):67-9.

Akt signaling mediates VEGF/VPF vascular permeability in vivo.

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Molecular Cardiology, Whitaker Cardiovascular Institute, Boston University School of Medicine, 715 Albany Street, W611, Boston, MA 02118-2526, USA.


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.

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