Akt-FOXO3a signaling affects human endothelial progenitor cell differentiation.

Here we address the effect of Akt signaling on endothelial progenitor cells (EPCs). Human peripheral blood mononuclear cells (PBMCs) were cultured on fibronectin-coated dishes in EPC differentiation medium. PBMCs differentiated in a series of three steps: proliferation for foci formation, tight attachment to the dishes in the early stages of differentiation, and maturation in the late stages. In Western blot analysis, Akt expression was attenuated in the early stages of differentiation and was gradually upregulated during EPC maturation. Forkhead box-containing protein, class O 3a (FOXO3a), an Akt downstream target, was downregulated through phosphorylation in the late stages of EPC differentiation. Adenovirus-mediated overexpression of activated FOXO3a in PBMCs markedly increased the number of cell foci but reduced the number of DiI-acetyl LDL EPCs that appear at later time points. These data suggest that Akt/FOXO3a signaling is an important regulator of EPC maturation.