title: Bone marrow rejuvenation accelerates re-endothelialization and attenuates intimal hyperplasia after vascular injury in aging mice.
abstract: 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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  EPCs play a critical role in vascular repair in aging mice. BM rejuvenation accelerates re-endothelialization by improving EPC function.
authors.affiliation: Heart Failure Research Center, Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital.
authors.forename: Chao-Hung
authors.initials: CH
authors.lastname: Wang
authors.forename: Ming-Feng
authors.initials: MF
authors.lastname: Lee
authors.forename: Ning-I
authors.initials: NI
authors.lastname: Yang
authors.forename: Hsiu-Fu
authors.initials: HF
authors.lastname: Mei
authors.forename: Sheng-Yuan
authors.initials: SY
authors.lastname: Lin
authors.forename: Wen-Chin
authors.initials: WC
authors.lastname: Cherng
mesh_terms: D000375:Aging / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D064591:Allografts; D000818:Animals; D016026:Bone Marrow Transplantation; D002465:Cell Movement / Q000235:genetics; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D051417:Focal Adhesion Kinase 1 / Q000235:genetics / Q000378:metabolism; D006965:Hyperplasia; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D013234:Stem Cells / Q000378:metabolism* / Q000473:pathology; D017539:Tunica Intima / Q000378:metabolism* / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D057772:Vascular System Injuries / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D019869:Phosphatidylinositol 3-Kinases; D051417:Focal Adhesion Kinase 1; C496051:Ptk2 protein, mouse; D051057:Proto-Oncogene Proteins c-akt