title: Lymphocyte cytotoxicity of oxLDL in patients with atherosclerosis.
abstract: BACKGROUND
  Atherosclerosis, a chronic inflammatory disease of the vessel wall, is characterized by local and systemic immune responses to a variety of antigens. Oxidized low-density lipoprotein (oxLDL) is considered as an important determining factor in the pathogenesis of atherosclerosis.
  
  
  OBJECTIVE
  The purpose of this study was to investigate the degree of peripheral blood mononuclear cells (PBMC) vulnerability to in vitro oxLDL-induced cytotoxicity from atherosclerotic patients in comparison to healthy individuals.
  
  
  METHODS
  Thirty patients with atherosclerotic lesions, confirmed by angiography, and 30 matched healthy individuals were investigated. PBMC was prepared from individuals' blood samples which were further stimulated with low dose (1 μg/mL) and high dose (50 μg/mL) of extensively oxidized LDL. MTT assay was utilized to measure cell viability and proliferation. Stimulation index (SI) was calculated as mean ratio of optical density (OD) of the stimulated cells divided by OD of untreated cells.
  
  
  RESULTS
  Low dose oxLDL treatment caused no significant proliferative or cytotoxic effect in the control group; however, similar treatment caused significant cytotoxic effect in the patients compared to the controls (p=0.026). High dose oxLDL treatment induced more significant cytotoxicity in the patients compared to the controls (p=0.006). Comparison of the SI between the two groups of patients and controls showed significantly lower index by either the low (p=0.03) or the high dose (p<0.001) oxLDL in the patients compared to the controls.
  
  
  CONCLUSIONS
  PBMC from patients with atherosclerosis showed increased susceptibility to oxLDL-induced cytotoxicity. Our results imply that prolonged exposure to elevated levels of circulating oxLDL could weaken the cellular defense mechanisms by progressive depletion of the pool of antiapoptotic proteins, rendering the cells more vulnerable to oxLDL-induced cell death.
authors.affiliation: Division of Cardiology, Department of Internal Medicine, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mohammad Jafar
authors.initials: MJ
authors.lastname: Mahmoudi
authors.forename: Maryam
authors.initials: M
authors.lastname: Mahmoudi
authors.forename: Fereydoon
authors.initials: F
authors.lastname: Siassi
authors.forename: Fazel
authors.initials: F
authors.lastname: Shokri
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Eshraghian
authors.forename: Amir Hassan
authors.initials: AH
authors.lastname: Zarnani
authors.forename: Reza
authors.initials: R
authors.lastname: Chahardoli
authors.forename: Mona
authors.initials: M
authors.lastname: Hedayat
authors.forename: Jalal
authors.initials: J
authors.lastname: Khoshnoodi
authors.forename: Hashem
authors.initials: H
authors.lastname: Nayeri
authors.forename: Nima
authors.initials: N
authors.lastname: Rezaei
authors.forename: Ali-Akbar
authors.initials: AA
authors.lastname: Saboor-Yaraghi
mesh_terms: D000328:Adult; D050197:Atherosclerosis / Q000276:immunology / Q000503:physiopathology*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects*; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged
chemical_list: D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein