Bone Marrow Rejuvenation Accelerates Re-Endothelialization and Attenuates Intimal Hyperplasia After Vascular Injury in Aging Mice

作者：Wang Chao Hung^*; Lee Ming Feng; Yang Ning I; Mei Hsiu Fu; Lin Sheng Yuan; Cherng Wen Chin

来源：Circulation Journal, 2013, 77(12): 3045-3053.

DOI：10.1253/circj.CJ-13-0267

• Aging
• Bone marrow rejuvenation
• Endothelial progenitor cells
• Intimal hyperplasia
• Re-endothelialization

Background: Aging-associated functional impairment of endothelial progenitor cells (EPCs) contributes to delayed re-endothelialization after vascular injury and exaggerated intimal hyperplasia (IH). This study tested if bone marrow (BM) rejuvenation accelerates post-injury re-endothelialization in aging mice. %26lt;br%26gt;Methods and Results: Using BM transplantation (BMTGfp -%26gt; Wild), young(GfP) to young(Wild) (YTY), old(GfP) to old(Wild) (OTO), young(GfP) to old(Wild) (YTO), and old(GfP) to young(Wild) (OTY) groups were created. After vascular injury, IH was significantly greater in the old group than the young group (P%26lt;0.001). BM rejuvenation (YTO) significantly accelerated re-endothelialization and attenuated IH. Compared with the OTO group, the YTY and YTO groups had earlier and greater EPC-derived re-endothelialization (P%26lt;0.001). The number of Sca-1(+)KDR(+) EPCs mobilized in the circulation induced by vascular injury was higher in young, YTO, and YTY mice than in old mice (P%26lt;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%26lt;0.05). The increase in blood vascular endothelial growth factor (VEGF) levels after vascular injury was higher in young than in old mice. PI3K, Akt, and FAK pathways played a pivotal role in VEGF-associated EPC migration. Specifically, EPCs from young and YTO mice, compared with old mice, demonstrated stronger FAK phosphorylation after VEGF stimulation. %26lt;br%26gt;Conclusions: EPCs play a critical role in vascular repair in aging mice. BM rejuvenation accelerates re-endothelialization by improving EPC function.

• 出版日期2013-12
• 单位长春大学