title: Apolipoprotein A-I mimetic peptide reverses impaired arterial healing after injury by reducing oxidative stress.
abstract: OBJECTIVE
  Endothelial cell (EC) migration is essential for healing of arterial injuries caused by angioplasty, but a high cholesterol diet inhibits endothelial repair. In vivo studies suggest that apolipoprotein A-I (apoA-I), the major protein constituent of HDL, is essential for normal healing of arterial injuries. ApoA-I mimetics, including 4F, have been designed to mimic the amphipathic portion of the apoA-I molecule. This study was undertaken to determine if 4F improves endothelial migration and healing.
  
  
  METHODS
  A razor scrape assay was used to analyze the effect of 4F on EC migration in vitro. Endothelial healing in vivo was assessed following electrical injury of carotid arteries in mice. Markers of oxidative stress were also examined.
  
  
  RESULTS
  Lipid oxidation products inhibited EC migration in vitro, but preincubation with L-4F preserved EC migration. Endothelial healing of carotid arterial injuries in mice on a high cholesterol diet was delayed compared with mice on a chow diet with 27.8% vs. 48.2% healing, respectively, at 5 days. Administration of D-4F improved endothelial healing in mice on a high cholesterol diet to 43.4%. D-4F administration had no effect on lipid levels but decreased markers of oxidation. In vivo, there was a significant inverse correlation between endothelial healing and plasma markers of oxidative stress.
  
  
  CONCLUSIONS
  These studies suggested that an apoA-I mimetic can improve endothelial healing of arterial injuries by decreasing oxidative stress.
authors.affiliation: Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, OH 44106, USA; Department of Biomedical Engineering, Cleveland Clinic, Cleveland, OH 44195, USA; Department of Vascular Surgery, Cleveland Clinic, Cleveland, OH 44195, USA. Electronic address: Michael.Rosenbaum@va.gov.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Rosenbaum
authors.affiliation: Department of Biomedical Engineering, Cleveland Clinic, Cleveland, OH 44195, USA.
authors.forename: Pinaki
authors.initials: P
authors.lastname: Chaudhuri
authors.affiliation: Department of Biomedical Engineering, Cleveland Clinic, Cleveland, OH 44195, USA.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Abelson
authors.affiliation: Department of Biomedical Engineering, Cleveland Clinic, Cleveland, OH 44195, USA; Novant Health, 1915 Randolph Road, Charlotte, NC 28207, USA.
authors.forename: Brandy N
authors.initials: BN
authors.lastname: Cross
authors.affiliation: Department of Biomedical Engineering, Cleveland Clinic, Cleveland, OH 44195, USA; Department of Vascular Surgery, Cleveland Clinic, Cleveland, OH 44195, USA.
authors.forename: Linda M
authors.initials: LM
authors.lastname: Graham
mesh_terms: D000818:Animals; D001011:Aorta / Q000166:cytology; D016632:Apolipoprotein A-I / Q000737:chemistry / Q000378:metabolism*; D001158:Arteries / Q000378:metabolism*; D002339:Carotid Arteries / Q000473:pathology; D002417:Cattle; D002465:Cell Movement; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology; D006937:Hypercholesterolemia / Q000473:pathology; D008055:Lipids / Q000737:chemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress; D010455:Peptides / Q000737:chemistry*; D010766:Phosphorylation; D017382:Reactive Oxygen Species / Q000378:metabolism; D013927:Thrombosis; D014945:Wound Healing
chemical_list: D016632:Apolipoprotein A-I; D008055:Lipids; D010455:Peptides; D017382:Reactive Oxygen Species; C582295:apolipoprotein A-I mimetic peptide 4F
keywords: Apolipoprotein A-I mimetic; Arterial healing; D-4F; Endothelial migration; Endothelium; Hypercholesterolemia; L-4F