title: The effect of senescence of endothelial progenitor cells on in-stent restenosis in patients undergoing coronary stenting.
abstract: OBJECTIVE
  Restenosis after stent implantation is caused by endothelial cell damage and subsequent neointimal formation. The objective of this study is to elucidate the relevance of endothelial progenitor cells (EPCs) in the development of in-stent restenosis in patients undergoing stent implantation.
  
  
  METHODS
  The subjects were 46 patients who underwent coronary stenting. Blood samples were collected at the time of follow-up coronary angiography after coronary stenting. EPCs were isolated from blood samples and cultured. Their phenotypes were confirmed by uptake of acetylated low-density lipoprotein and binding of fluorescein isothiocyanate-labeled Ulex europaeus agglutinin 1 lectin. The number of colony-forming units (CFUs) and the senescent cells, determined by acidic beta-galactosidase staining, was counted. Angiogenic growth factors secreted by EPCs, such as vascular endothelial growth factor (VEGF), basic fibroblast growth factor (b-FGF), hepatocyte growth factor (HGF), and macrophage chemoattractant protein (MCP-1) from the culture medium were also measured by enzyme-linked immunosorbent assay.
  
  
  RESULTS
  Patients with in-stent restenosis (defined as >40% stenosis, n=16) had a decreased number of CFUs (p<0.05), and increased senescent cells (p<0.05), compared to patients without restenosis (n=30). There was no significant difference of angiogenic growth factors (VEGF, HGF, b-FGF, and MCP-1) secreted by EPCs between the two groups. On multivariate analysis, an increased number of senescent EPCs was the indepen-dent factor associated with in-stent restenosis (OR 1.10, 95% CI 1.01 to 1.20).
  
  
  CONCLUSIONS
  These data suggested that EPCs might be involved in the development of in-stent restenosis.
authors.affiliation: Department of Cardiovascular Medicine, Wakayama Medical University, Wakayama.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Matsuo
authors.forename: Toshio
authors.initials: T
authors.lastname: Imanishi
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Hayashi
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Tomobuchi
authors.forename: Takashi
authors.initials: T
authors.lastname: Kubo
authors.forename: Takuzo
authors.initials: T
authors.lastname: Hano
authors.forename: Takashi
authors.initials: T
authors.lastname: Akasaka
mesh_terms: D000368:Aged; D043925:Angiogenesis Inducing Agents / Q000378:metabolism; D002478:Cells, Cultured; D016922:Cellular Senescence; D003324:Coronary Artery Disease / Q000097:blood / Q000628:therapy*; D023903:Coronary Restenosis / Q000209:etiology*; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology; D015607:Stents
chemical_list: D043925:Angiogenesis Inducing Agents