Akt signaling mediates VEGF/VPF vascular permeability in vivo

FEBS Letters

Walsh, Kenneth²  Six, Isabelle²  Kureishi, Yasuko¹  Luo, Zhengyu³ 

[1] Medicine I, Cardiovascular Division, Mie University School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan;Molecular Cardiology, Whitaker Cardiovascular Institute, Boston University School of Medicine, 715 Albany Street, W611, Boston, MA 02118-2526, USA;Genzyme, 31 New York Avenue, Framingham, MA 01701-9322, USA

关键词: Akt;    Cytokine;    Angiogenesis;    Endothelial cells;    Gene transfer;    Signaling;    VEGF;    vascular endothelial growth factor;    VPF;    vascular permeability factor;    eNOS;    endothelial cell nitric oxide synthase;    PI 3-kinase;    phosphatidylinositol 3-kinase;   

DOI  :  10.1016/S0014-5793(02)03630-X

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown