title: Oxidative stress, DNA damage and repair in heart failure patients after implantation of continuous flow left ventricular assist devices.
abstract: OBJECTIVE
  To study the status of oxidative stress and DNA damage repair in circulating blood leukocytes of heart failure patients supported by continuous flow left ventricular assist devices (LVADs).
  
  
  METHODS
  Ten HF patients implanted with LVAD as bridge to transplant or destination therapy were enrolled in the study and 10 age and sex matched volunteers were recruited as the study control. Reactive oxygen species (ROS) in blood leukocytes and superoxide dismutase (SOD) in erythrocytes were measured by flow cytometry/immunofluorescence microscopy and spectrophotometry, respectively. ELISA was used to measure oxidized low density lipoproteins (oxLDL) in plasma. Markers of DNA damage (γ-H2AX) and repairs (Mre11, DNA ligase IV, Ku70, and Ku80) were quantified in blood lymphocytes by immunocytochemistry.
  
  
  RESULTS
  Levels of ROS and oxLDL were significantly higher in HF patients with LVAD than baseline as well as the control group; moreover, SOD levels were decreased with increasing post-operative periods. All the changes indicated enhanced oxidative stress among LVAD recipients. Significantly higher γ-H2AX foci in lymphocytes confirmed DNA double strand breaks in LVAD recipients. γ-H2AX foci numbers in lymphocytes were positively correlated with the ROS and oxLDL and negatively with SOD levels (p<0.0001). Expressions of DNA ligase IV, Ku70 and Ku80 proteins were highest after one week and Mre11 protein after 3 months of LVAD transplantation; indicated abnormal DNA repair.
  
  
  CONCLUSIONS
  The study, for the first time shows that, continuous flow LVAD implanted HF patients not only exhibit elevated oxidative stress and DNA damage in blood leukocytes but also have abnormalities in DNA repair pathways.
authors.affiliation: Department of Surgery, Artificial Organ Lab, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
authors.forename: Nandan Kumar
authors.initials: NK
authors.lastname: Mondal
authors.forename: Erik
authors.initials: E
authors.lastname: Sorensen
authors.forename: Nicholas
authors.initials: N
authors.lastname: Hiivala
authors.forename: Erika
authors.initials: E
authors.lastname: Feller
authors.forename: Bartley
authors.initials: B
authors.lastname: Griffith
authors.forename: Zhongjun Jon
authors.initials: ZJ
authors.lastname: Wu
mesh_terms: D000368:Aged; D004249:DNA Damage; D004260:DNA Repair; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006333:Heart Failure / Q000235:genetics / Q000378:metabolism / Q000601:surgery*; D006353:Heart-Assist Devices; D006801:Humans; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase
keywords: DNA damage; DNA repair.; heart failure; left ventricular assist device; oxidative stress