Heart Failure Research Center, Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital.
Circ J. 2013;77(12):3045-53. doi: 10.1253/circj.cj-13-0267. Epub 2013 Sep 13.
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.
Using BM transplantation (BMT(Gfp→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<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<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<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 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.
EPCs play a critical role in vascular repair in aging mice. BM rejuvenation accelerates re-endothelialization by improving EPC function.
与衰老相关的内皮祖细胞（EPCs）功能障碍导致血管损伤后再内皮化延迟和内膜过度增生（IH）。本研究测试了骨髓（BM）年轻化是否能加速衰老小鼠损伤后的再内皮化。
通过骨髓移植（BMT（Gfp→Wild）），建立了年轻（Gfp）到年轻（Wild）（YTY）、年老（Gfp）到年老（Wild）（OTO）、年轻（Gfp）到年老（Wild）（YTO）和年老（Gfp）到年轻（Wild）（OTY）组。血管损伤后，老年组 IH 明显大于年轻组（P<0.001）。BM 年轻化（YTO）显著加速再内皮化并减轻 IH。与 OTO 组相比，YTY 和 YTO 组的 EPC 衍生再内皮化更早、更大（P<0.001）。血管损伤诱导的循环中 Sca-1（+）KDR（+）EPC 的动员数量在年轻、YTO 和 YTY 小鼠中高于老年小鼠（P<0.05）。年轻、YTO 和 YTY 组的 Sca-1（+）BM 细胞的迁移和黏附能力强于老年组（P<0.05）。血管损伤后血液血管内皮生长因子（VEGF）水平的升高在年轻小鼠中高于老年小鼠。PI3K、Akt 和 FAK 通路在 VEGF 相关 EPC 迁移中发挥关键作用。具体来说，与老年小鼠相比，年轻和 YTO 小鼠的 EPC 在 VEGF 刺激后表现出更强的 FAK 磷酸化。
EPCs 在衰老小鼠的血管修复中发挥关键作用。BM 年轻化通过改善 EPC 功能加速再内皮化。
