Abstract 11554: Bone Marrow Rejuvenation Accelerates Re-endothelialization In Aging Mice After Vascular Injury
Background: Aging-associated impairment of the biological function of endothelial progenitor cells (EPCs) contributes to delayed re-endothelialization after vascular injury and exaggerated intimal hyperplasia (IH).
Objectives: This study tested if bone marrow (BM) rejuvenation accelerates re-endothelialization in aging mice after vascular injury.
Methods and results: Mice at the ages of 2 and 18 months were respectively used as young and old mice. Using BM transplantation (BMTGfp®Wild), youngGfp to youngWild (YTY), oldGfp to oldWild (OTO), youngGfp to oldWild (YTO), and oldGfp to youngWild (OTY) groups were created. After wire injury, IH of the femoral artery on day 28 was significantly greater in the old group than the young group (p<0.001). BM rejuvenation in old mice (YTO) significantly accelerated re-endothelialization and attenuated IH. Compared to the OTO group, the YTY and YTO groups had earlier and greater EPC-derived re-endothelialization (p<0.001). The number of Sca-1+KDR+ EPCs mobilized in the circulation induced by hindlimb ischemia was higher in young, YTO, and YTY mice than in old mice (p<0.05). Sca-1+ BM cells from the young, YTO, and YTY groups had better migration and adhesion capacities than those from the old group (p<0.05). The increase in blood vascular endothelial growth factor (VEGF) levels after hindlimb ischemia was higher in young than old mice. Compared to old mice, Sca-1+ BM cells from young and YTO mice demonstrated higher levels of focal adhesion kinase and Akt phosphorylation after activation by VEGF.
Conclusions: BM rejuvenation accelerates re-endothelialization after vascular injury in aging mice by increasing EPC migration, mobilization, and adhesion.
- © 2012 by American Heart Association, Inc.