Περίληψη:
Angiopoietin-2 (Ang2) is a Tie-2 ligand that destabilizes vascular
structures, allowing for neovascularization or vessel regression
depending on local vascular endothelial cell growth factor (VEGF)
concentrations. Although various stimuli have been shown to affect Ang2
expression, information on the underlying mechanisms involved in Ang2
production in endothelial cells (EC) is just beginning to emerge. In the
present study, we have used adenovirus-mediated gene transfer and
pharmacological inhibitors to examine the role of the PTEN/PI3-K/Akt
pathway on Ang2 release. Inhibition of PI3-kinase with wortmannin led to
a stimulation of basal Ang2 release in EC, while overexpression of an
active form of Akt reduced Ang2. in addition, adenovirus-mediated gene
transfer of the phosphatase PTEN stimulated Ang2 release. Incubation of
the cells with Ang1, an agent that activates the PI3-K/Akt pathway in
EC, reduced Ang2 release. This effect of Ang1 Could be prevented by
wortmannin and LY-294002 pretreatment. Similarly, in VEGF-treated EC the
increase in Ang2 production observed was greater in the presence of a
PI3-K inhibitor. Our observations that PTEN acts as a positive modulator
of Ang2 release, while activation of the PI3-K/Akt pathway downregulates
Ang2, reveal an additional mechanism through which the PTEN/PI3-K/Akt
pathway could affect the angiogenic process.
Συγγραφείς:
Tsigkos, S
Zhou, ZM
Kotanidou, A
Fulton, D
Zakynthinos,
S
Roussos, C
Papapetropoulos, A
