title: Vitamin A Decreases Cytotoxicity of Oxidized Low-Density Lipoprotein in Patients with Atherosclerosis.
abstract: BACKGROUND
  Oxidized low-density lipoprotein (ox-LDL) is implicated in initiation and progression of atherosclerosis. Previously, we found that ox-LDL increases vulnerability of peripheral blood mononuclear cells (PBMCs) in atherosclerotic patients compared to controls. Vitamin A induces proliferation of PBMCs. The aim of this study was to determine the effect of vitamin A supplementation on PBMC survival against LDL and different doses of ox-LDL.
  
  
  METHODS
  In this double-blind placebo-controlled trial, we recruited 35 atherosclerotic patients and 38 healthy controls and randomly allocated them into placebo and vitamin A groups, which received either placebo or 25,000 IU/day of vitamin A for 3 months. PBMCs were isolated, cultured, and stimulated by 1 µg/mL LDL as well as 1 µg/mL and 50 µg/mL ox-LDL. The stimulation indexes (SIs) of PBMCs were calculated to identify cell viability. Additionally, the circulating ox-LDL levels were measured by ELISA.
  
  
  RESULTS
  Viability of PBMCs stimulated by 50 µg/mL ox-LDL significantly increased following vitamin A supplementation in patients (p < 0.01). The levels of circulating ox-LDL were not changed by vitamin A treatment. Ox-LDL levels were strongly and positively correlated to SI of PBMCs stimulated by 1 µg/mL LDL and1 µg/mL ox-LDL in all groups.
  
  
  CONCLUSIONS
  Vitamin A decreases cytotoxicity of high-dose ox-LDL and improves PBMC viability. The protective effect of vitamin A is not mediated by an antioxidative mechanism, but may instead have been due to intracellular protection of the apoptotic machinery or induction of proliferation of the cells. Higher levels of ox-LDL increase PBMC irritability in all participants.
authors.affiliation: a Division of Cardiology, Department of Internal Medicine , Tehran University of Medical Sciences , Tehran , Iran.
authors.forename: Mohammad Jafar
authors.initials: MJ
authors.lastname: Mahmoudi
authors.affiliation: b Department of Cellular Molecular Nutrition , School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences , Tehran , Iran.
authors.forename: Ali-Akbar
authors.initials: AA
authors.lastname: Saboor-Yaraghi
authors.affiliation: b Department of Cellular Molecular Nutrition , School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences , Tehran , Iran.
authors.forename: Fateme
authors.initials: F
authors.lastname: Zabetian-Targhi
authors.affiliation: c Department of Community Nutrition , School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences , Tehran , Iran.
authors.forename: Fereydoon
authors.initials: F
authors.lastname: Siassi
authors.affiliation: d Nanobiotechnology Research Center , Avicenna Research Institute, ACECR , Tehran , Iran.|e Immunology Research Center, Faculty of Medicine , Iran University of Medical Sciences , Tehran , Iran.
authors.forename: Amir Hassan
authors.initials: AH
authors.lastname: Zarnani
authors.affiliation: f Department of Biostatistics , School of Public Health, Tehran University of Medical Sciences , Tehran , Iran.
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Eshraghian
authors.affiliation: g Department of Immunology , School of Public Health, Tehran University of Medical Sciences , Tehran , Iran.
authors.forename: Fazel
authors.initials: F
authors.lastname: Shokri
authors.affiliation: h Molecular Immunology Research Center, Department of Immunology , School of Medicine, Tehran University of Medical Sciences , Tehran , Iran.|i Research Group for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center , Tehran University of Medical Sciences , Tehran , Iran.
authors.forename: Nima
authors.initials: N
authors.lastname: Rezaei
authors.affiliation: b Department of Cellular Molecular Nutrition , School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences , Tehran , Iran.
authors.forename: Yas
authors.initials: Y
authors.lastname: Kalikias
authors.affiliation: b Department of Cellular Molecular Nutrition , School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences , Tehran , Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Mahmoudi
mesh_terms: D000328:Adult; D000368:Aged; D050197:Atherosclerosis / Q000378:metabolism*; D016022:Case-Control Studies; D002470:Cell Survival / Q000187:drug effects; D015897:Comorbidity; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism* / Q000633:toxicity; D008875:Middle Aged; D012307:Risk Factors; D014801:Vitamin A / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D014801:Vitamin A
keywords: Atherosclerosis; cell viability; cytotoxicity; oxidized LDL; peripheral blood mononuclear cells; vitamin A