title: Impaired graft healing due to hypercholesterolemia is prevented by dietary supplementation with alpha-tocopherol.
abstract: OBJECTIVE
  The patency of prosthetic grafts is partly limited by incomplete endothelial cell coverage and development of anastomotic intimal hyperplasia. The goal of this study was to determine the effect of elevated cholesterol on prosthetic graft healing and the ability of alpha-tocopherol to improve healing.
  
  
  METHODS
  Rabbits were placed on one of four diets: chow, chow plus 1% cholesterol, chow plus alpha-tocopherol, or chow plus 1% cholesterol and alpha-tocopherol. After 2 weeks, expanded polytetrafluoroethylene grafts (12-cm long, 4-mm internal diameter) were implanted in the abdominal aorta. Grafts were removed after 6 weeks and analyzed for cholesterol and alpha-tocopherol content, endothelial coverage, anastomotic intimal thickness, and cellular composition of the neointima.
  
  
  RESULTS
  At the time of graft implantation, plasma cholesterol was 34 +/- 4 mg/dL in the chow group and 689 +/- 30 mg/dL in the 1% cholesterol group (P < .05). Grafts removed from hypercholesterolemic rabbits had marked intimal thickening, with an intima/graft thickness ratio of 0.76 +/- 0.29 compared with 0.14 +/- 0.06 in chow animals (P < .05). Macrophage infiltrate was increased to 45 +/- 11 macrophages/0.625 mm(2) in grafts from hypercholesterolemic rabbits compared with 0 +/- 0.4 in controls (P < .05). Endothelialization of grafts was lower in hypercholesterolemic rabbits than in the chow group, with endothelial cells covering 46% +/- 7% and 62% +/- 7% of the graft surface, respectively (P = .05). When alpha-tocopherol was added to the 1% cholesterol diet, the macrophage count decreased to 12 +/- 8, the intimal/graft thickness ratio decreased to 0.17 +/- 0.09, and endothelial coverage increased to 70% +/- 7% (P < .05 compared with the high-cholesterol group).
  
  
  CONCLUSIONS
  Anastomotic intimal hyperplasia is dramatically increased and endothelialization is reduced in rabbits on a high-cholesterol diet, but alpha-tocopherol supplementation blocks the augmented neointimal thickening and improves endothelial cell coverage.
authors.affiliation: Department of Biomedical Engineering, Cleveland Clinic, Cleveland, Ohio, USA.
authors.forename: Keiko
authors.initials: K
authors.lastname: Miyazaki
authors.forename: Scott M
authors.initials: SM
authors.lastname: Colles
authors.forename: Linda M
authors.initials: LM
authors.lastname: Graham
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001807:Blood Vessel Prosthesis; D019587:Dietary Supplements; D042783:Endothelial Cells; D004730:Endothelium, Vascular / Q000254:growth & development; D006937:Hypercholesterolemia / Q000150:complications*; D006965:Hyperplasia; D011183:Postoperative Complications / Q000209:etiology* / Q000517:prevention & control*; D011817:Rabbits; D015607:Stents; D017539:Tunica Intima / Q000473:pathology; D024502:alpha-Tocopherol / Q000627:therapeutic use*
chemical_list: D000975:Antioxidants; D024502:alpha-Tocopherol