title: Increased oxidative stress in foam cells obtained from hemodialysis patients.
abstract: Premature atherosclerosis represents the main cause of mortality among end-stage renal disease patients (ESRD). Increased inflammation and oxidative stress are involved in initiation and progression of the atherosclerotic plaque. As foam cells are capable of producing significant amounts of inflammatory mediators and free radicals, we hypothesized that foam cells from uremic patients could produce more inflammation and oxidative stress than foam cells from normal people and be, somehow, involved in the accelerated atherosclerosis of uremia. To test this hypothesis, the levels of a few markers of inflammation and oxidative stress: Tumor necrosis factor-α, inducible nitric oxide synthase, malondialdehyde, nitric oxide by-products were measured in the supernatants of macrophage-derived foam cells cultures from 18 hemodialysis patients and 18 apparently healthy individuals controls. Malondialdehyde levels in the supernatant of cell cultures (macrophages stimulated or not with native and oxidized lipoprotein) were significantly increased in uremic patients; no statistically significant difference was found between the supernatant concentrations of nitric oxide by-products, inducible nitric oxide synthase activity, and tumor necrosis factor-α between patients and controls. Our results, obtained with human macrophages and macrophage-derived foam cells, are compatible with the theory that increased cellular oxidative stress and inflammatory activity in ESRD patients could accelerate the atherosclerotic process. The present culture protocol showed it is possible to use human mononuclear cells to evaluate the oxidative metabolism of foam cells, which are considered to be the initial step of atherosclerotic lesions.
authors.affiliation: Histocompatibility Laboratory, State University of Londrina, Londrina, PR, Brazil.
authors.forename: Marlene S B
authors.initials: MS
authors.lastname: Gonçalves
authors.forename: Bruno A
authors.initials: BA
authors.lastname: Fabris
authors.forename: Francis F
authors.initials: FF
authors.lastname: Brinholi
authors.forename: Chiara C
authors.initials: CC
authors.lastname: Bortolasci
authors.forename: Maria A E
authors.initials: MA
authors.lastname: Watanabe
authors.forename: Karen B
authors.initials: KB
authors.lastname: Oliveira
authors.forename: Vinícius D A
authors.initials: VD
authors.lastname: Delfino
authors.forename: Edson L
authors.initials: EL
authors.lastname: Lavado
authors.forename: Décio S
authors.initials: DS
authors.lastname: Barbosa
mesh_terms: D000328:Adult; D050197:Atherosclerosis / Q000378:metabolism / Q000473:pathology; D002097:C-Reactive Protein / Q000378:metabolism; D016022:Case-Control Studies; D002478:Cells, Cultured; D005260:Female; D005487:Foam Cells / Q000378:metabolism* / Q000473:pathology; D015870:Gene Expression; D006801:Humans; D007676:Kidney Failure, Chronic / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D006435:Renal Dialysis / Q000009:adverse effects* / Q000379:methods; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D002097:C-Reactive Protein; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II