title: Oxidative stress - a link between endothelial injury, coagulation activation, and atherosclerosis in haemodialysis patients.
abstract: OBJECTIVE
  Recently emerging evidence suggests that oxidative stress (SOX) may participate in atherogenesis. The aim of the present study was to establish whether enhanced SOX, involving endothelial injury, activation of coagulation, and inflammatory reaction, could be implicated in atherosclerotic diseases in haemodialysis (HD) patients.
  
  
  METHODS
  Markers of SOX, endothelial injury, coagulation, and cytokines, were measured in the plasma of HD patients with and without cardiovascular disease (CVD), and of healthy controls by ELISA methods. Remodeling of the carotid arteries was assessed by measuring the intima-media thickness (IMT) as a surrogate of atherosclerotic disease in all groups.
  
  
  RESULTS
  Markers of SOX, endothelial injury, and extrinsic coagulation pathway activation and IMT values were significantly elevated in HD patients, especially in those with CVD when compared with the control group. The von Willebrand factor antigen (vWF:Ag) levels were more increased in the patients with CVD than in those without. Furthermore, the plasma levels of tumour necrosis factor alpha, monocyte chemo-attractant protein 1, and macrophage inflammatory protein 1 beta were significantly higher only in the HD group with CVD when compared with the controls. The IMT was strongly and directly correlated with Cu/Zn superoxide dismutase. Both IMT and Cu/Zn superoxide dismutase were positively correlated with age, thrombomodulin, vWF:Ag, tissue factor, tissue factor pathway inhibitor, prothrombin fragment F1 + 2, monocte chemo-attractant protein 1, macrophage inflammatory protein 1 beta, and tumour necrosis factor alpha levels. Multivariate analysis identified vWF:Ag as the only independent variable significantly associated with an increased IMT.
  
  
  CONCLUSIONS
  The present study suggests that enhanced SOX, involved pro-atherogenic cytokine and chemokines levels, endothelial injury, and coagulation activation may constitute a pathway for accelerated atherosclerosis in HD patients. The significant, independent association between IMT and vWF:Ag should be assessed in future studies to determine whether vWF:Ag elevation is causative or a by-product of the increased IMT.
authors.affiliation: Department of Nephrology and Clinical Transplantation, Medical University, Białystok, Poland. krystynapawlak@poczta.onet.pl
authors.forename: Krystyna
authors.initials: K
authors.lastname: Pawlak
authors.forename: Beata
authors.initials: B
authors.lastname: Naumnik
authors.forename: Szymon
authors.initials: S
authors.lastname: Brzósko
authors.forename: Dariusz
authors.initials: D
authors.lastname: Pawlak
authors.forename: Michał
authors.initials: M
authors.lastname: Myśliwiec
mesh_terms: D015415:Biomarkers / Q000097:blood; D001777:Blood Coagulation; D001794:Blood Pressure; D016022:Case-Control Studies; D018925:Chemokines / Q000097:blood; D003324:Coronary Artery Disease / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000097:blood; D004730:Endothelium, Vascular / Q000293:injuries* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D015227:Lipid Peroxidation; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D018384:Oxidative Stress; D006435:Renal Dialysis / Q000009:adverse effects*
chemical_list: D015415:Biomarkers; D018925:Chemokines; D016207:Cytokines; D018836:Inflammation Mediators; D008055:Lipids