Young environment reverses the declined activity of aged rat-derived endothelial progenitor cells: involvement of the phosphatidylinositol 3-kinase/Akt signaling pathway.

BACKGROUND: Although age-related impairment of endothelial progenitor cells (EPCs) has been documented in recent studies, the detailed role of aging-induced environment in EPCs remains unclear. METHODS: Two and 20 months old Sprague-Dawley female rats were used in the present study. EPCs isolated from young (YEPCs) and aged (AEPCs) rats were cultured with young or aged serum. EPC migration and proliferation were detected with a modified Boyden chamber and the MTT assay, respectively; EPC differentiation was detected by reverse-transcription polymerase chain reaction or fluorescence-activated cell sorting; Akt and phosphorylated-Akt protein expression was detected with Western blotting. EPC transplantation was performed in the rat carotid artery injury models. RESULTS: Young serum significantly promotes AEPC migration, proliferation, and differentiation and increases phosphatidylinositol 3-kinase (PI3-K) and endothelial nitric oxide synthase activity in AEPCs compared with aged serum; total-Akt and phosphorylated-Akt protein expressions in AEPCs are also significantly upregulated by young serum. Transplanted AEPC numbers at vascular injury sites in the young rat carotid artery injury model significantly increased compared with those in aged models. Those effects could be reasonably attenuated by the PI3-K-specific blocker wortmannin. CONCLUSION: A young environment partly restores the declined AEPC activity and promotes AEPC homing to vascular injury sites; activation of the PI3-K/Akt signaling pathway is at least partly responsible for this process.