MRI detection of Rapamycin and AP-Cav therapeutic rescue from endothelial over expression of Akt in transgenic mice
Phung T, Ziv K, Brenner O, Neeman M, Benjamin L, Walsh K
Beth Israel Deaconess Medical Center and Harvard Medical School
Akt, a serine/threonine protein kinase is chronically activated in VEGF stimulated endothelial cells, and induces angiogenesis via its downstream effectors, mTOR and eNOS. MRI was applied here for studying the effect of pharmacological inhibition of mTOR and eNOS on myrAkt-activated vasodilation and elevation of blood volume, in a transgenic mouse model with endothelial inducible expression of dominant active Akt (myrAkt). Rapamycin (mTOR inhibitor) reduced blood volume to a normal level, while AP-Cav (eNOS inhibitor) yielded a smaller un-significant effect. Thus, suppressing the signaling of Akt via mTOR can reverse the angiogenic phenotype of tumor blood vessels induced by VEGF.