title: Vitamin E reduces progression of atherosclerosis in low-density lipoprotein receptor-deficient mice with established vascular lesions.
abstract: BACKGROUND
  A growing body of evidence from animal studies supports the hypothesis that oxidative stress-mediated mechanisms play a central role in early atherogenesis. In contrast, clinical trials with antioxidant vitamins have not produced consistent results in humans with established atherosclerosis.
  
  
  RESULTS
  Low-density lipoprotein receptor-deficient mice (LDLR KO) were fed a high-fat diet for 3 months to induce atheroma. At this time, 1 group of mice was euthanized for examination of atherosclerosis, and 2 other groups were randomized to receive high-fat diet either alone or supplemented with vitamin E for 3 additional months. At the end of the study, LDLR KO on a vitamin E-supplemented fat diet had decreased 8,12-iso-isoprostane (iP)F(2alpha)-VI and monocyte chemoattractant protein-1 levels, but increased nitric oxide levels compared with mice on placebo. No difference in lipid levels was observed between the 2 groups. Compared with baseline, placebo group had progression of atherosclerosis. In contrast, vitamin E-treated animals showed a significant reduction in progression of atherosclerosis.
  
  
  CONCLUSIONS
  These results demonstrate that in LDLR KO, vitamin E supplementation reduces progression of established atherosclerosis by suppressing oxidative and inflammatory reactions and increasing nitric oxide levels.
authors.affiliation: Center for Experimental Therapeutics and Department of Pharmacology, University of Pennsylvania, School of Medicine, Philadelphia, Pa 19104, USA.
authors.forename: Tillmann
authors.initials: T
authors.lastname: Cyrus
authors.forename: Yuemang
authors.initials: Y
authors.lastname: Yao
authors.forename: Joshua
authors.initials: J
authors.lastname: Rokach
authors.forename: Lina X
authors.initials: LX
authors.lastname: Tang
authors.forename: Domenico
authors.initials: D
authors.lastname: Praticò
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000473:pathology; D001161:Arteriosclerosis / Q000188:drug therapy* / Q000473:pathology; D015415:Biomarkers / Q000097:blood; D002784:Cholesterol / Q000097:blood; D004041:Dietary Fats / Q000009:adverse effects; D019587:Dietary Supplements; D015237:Dinoprost / Q000031:analogs & derivatives* / Q000097:blood; D018450:Disease Progression; D007150:Immunohistochemistry; D015227:Lipid Peroxidation / Q000187:drug effects; D051379:Mice; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000378:metabolism; D011973:Receptors, LDL / Q000172:deficiency* / Q000235:genetics; D016896:Treatment Outcome; D014280:Triglycerides / Q000097:blood; D014810:Vitamin E / Q000097:blood / Q000627:therapeutic use*
chemical_list: C115626:8,12-iso-isoprostane F2alpha-VI; D015415:Biomarkers; D004041:Dietary Fats; D011973:Receptors, LDL; D014280:Triglycerides; D014810:Vitamin E; D009569:Nitric Oxide; D002784:Cholesterol; D015237:Dinoprost