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Signaling pathways in angiogenesis

Keren Ziv , Thuy Phung, Laura E. Benjamin and Michal Neeman

Akt, a serine/threonine protein kinase is activated in endothelial cells by many angiogenic factors, and thus is chronically activated in an angiogenic environment. We have used a binary transgenic mouse model that expresses dominant active Akt (myrAkt) in endothelial cells in an inducible manner to investigate by MRI the effects of sustained endothelial Akt activation on vascular structure and function. Our data revealed that, Akt overexpression results in significant vasodilatation of blood vessels and in elevated permeability. Thus, signaling via Akt can account for the angiogenic phenotype of tumor blood vessels induced by VEGF.
Further studies using this transgenic model are aimed to explore the role of mTOR as a mediator of the angiogenic response through Akt pathway and the lymphatic system response to angiogenic and permeable environment, which is created due to Akt overexpression in endothelial cells.

Illustration of the contrast agent spread

Overlay of maximal intensity projections maps from images that were taken prior to CA injection (gray) and immediately after CA injection (color). Control mice - A,
myrAkt expressing mice - B.