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

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概要

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• 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. Methods and Results: 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 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. Conclusions: EPCs play a critical role in vascular repair in aging mice. BM rejuvenation accelerates re-endothelialization by improving EPC function.

著者

• Lee Ming-Feng

  Heart Failure Center, Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital

• Yang Ning-I

  Heart Failure Center, Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University College of Medicine

• Wang Chao-Hung

  Heart Failure Center, Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital

• Mei Hsiu-Fu

  Heart Failure Research Center, Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital

• Lin Sheng-Yuan

  Heart Failure Research Center, Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital

• Cherng Wen-Chin

  Heart Failure Research Center, Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital

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• Non-Invasive Cardiac Index Monitoring During Cardiopulmonary Functional Testing Provides Additional Prognostic Value in Patients After Acute Heart Failure
• Bone Marrow Rejuvenation Accelerates Re-Endothelialization and Attenuates Intimal Hyperplasia After Vascular Injury in Aging Mice

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