title: Low Circulating Levels of Mitochondrial and High Levels of Nuclear DNA Predict Mortality in Chronic Heart Failure.
abstract: BACKGROUND
  Mitochondrial DNA (mtDNA) and possibly nuclear DNA (nDNA) are released as danger-associated molecular patterns during cardiac stress, and may activate several innate immune receptors. The purpose of this study was to investigate the regulation of these danger-associated molecular patterns during human heart failure (HF).
  
  
  RESULTS
  Plasma levels of mtDNA and nDNA from HF patients (n = 84) were analyzed by reverse transcriptase-polymerase chain reaction and compared with controls (n = 72). Increased levels of mtDNA were found in New York Heart Association (NYHA) I-II and NYHA III-IV. There was evidence of increased nDNA in NYHA III-IV compared with controls and NYHA I-II. Kaplan-Meier analysis revealed higher mortality in patients with high nDNA levels, whereas high levels of mtDNA were associated with survival.
  
  
  CONCLUSIONS
  Plasma levels of mtDNA and nDNA are elevated in human HF associated with increased and decreased mortality, respectively. This study may suggest a rationale for exploring interventions within inflammatory signaling pathways activated by nucleic acids as novel targets in treatment of HF.
authors.affiliation: Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway; Center for Heart failure Research, University of Oslo, Oslo, Norway; K.G. Jebsen Inflammation Research Center, University of Oslo, Oslo, Norway; Faculty of Medicine, University of Oslo, Norway. Electronic address: yangched@gmail.com.
authors.forename: Yangchen
authors.initials: Y
authors.lastname: Dhondup
authors.affiliation: Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway; Faculty of Medicine, University of Oslo, Norway.
authors.forename: Thor
authors.initials: T
authors.lastname: Ueland
authors.affiliation: Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway; Center for Heart failure Research, University of Oslo, Oslo, Norway; Department of Cardiology, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
authors.forename: Christen Peder
authors.initials: CP
authors.lastname: Dahl
authors.affiliation: Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway; Center for Heart failure Research, University of Oslo, Oslo, Norway.
authors.forename: Erik Tandberg
authors.initials: ET
authors.lastname: Askevold
authors.affiliation: Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway; Center for Heart failure Research, University of Oslo, Oslo, Norway; K.G. Jebsen Inflammation Research Center, University of Oslo, Oslo, Norway; Faculty of Medicine, University of Oslo, Norway.
authors.forename: Øystein
authors.initials: Ø
authors.lastname: Sandanger
authors.affiliation: Faculty of Medicine, University of Oslo, Norway; Department of Cardiothoracic Surgery, Oslo University Hospital Rikshospitalet, Oslo, Norway.
authors.forename: Arnt
authors.initials: A
authors.lastname: Fiane
authors.affiliation: Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway; Center for Heart failure Research, University of Oslo, Oslo, Norway; K.G. Jebsen Inflammation Research Center, University of Oslo, Oslo, Norway.
authors.forename: Ingrid Kristine
authors.initials: IK
authors.lastname: Ohm
authors.affiliation: Center for Heart failure Research, University of Oslo, Oslo, Norway; Institute for Experimental Research, Oslo University Hospital, Ullevål, Oslo, Norway.
authors.forename: Ivar
authors.initials: I
authors.lastname: Sjaastad
authors.affiliation: Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway; Center for Heart failure Research, University of Oslo, Oslo, Norway; K.G. Jebsen Inflammation Research Center, University of Oslo, Oslo, Norway.
authors.forename: Alexandra Vanessa
authors.initials: AV
authors.lastname: Finsen
authors.affiliation: Center for Heart failure Research, University of Oslo, Oslo, Norway; Institute for Experimental Research, Oslo University Hospital, Ullevål, Oslo, Norway.
authors.forename: Anne
authors.initials: A
authors.lastname: Wæhre
authors.affiliation: Center for Heart failure Research, University of Oslo, Oslo, Norway; Faculty of Medicine, University of Oslo, Norway; Department of Cardiology, Oslo University Hospital, Rikshospitalet, Oslo, Norway; K.G. Jebsen Cardiovascular Research Center, University of Oslo, Oslo, Norway.
authors.forename: Lars
authors.initials: L
authors.lastname: Gullestad
authors.affiliation: Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway; K.G. Jebsen Inflammation Research Center, University of Oslo, Oslo, Norway; Faculty of Medicine, University of Oslo, Norway; Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
authors.forename: Pål
authors.initials: P
authors.lastname: Aukrust
authors.affiliation: Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway; Center for Heart failure Research, University of Oslo, Oslo, Norway; K.G. Jebsen Inflammation Research Center, University of Oslo, Oslo, Norway; Faculty of Medicine, University of Oslo, Norway.
authors.forename: Arne
authors.initials: A
authors.lastname: Yndestad
authors.affiliation: Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway; Center for Heart failure Research, University of Oslo, Oslo, Norway; Department of Cardiology, Oslo University Hospital, Rikshospitalet, Oslo, Norway; Department of Internal Medicine, Diakonhjemmet Hospital, Oslo, Norway.
authors.forename: Leif Erik
authors.initials: LE
authors.lastname: Vinge
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D056970:Co-Repressor Proteins / Q000378:metabolism*; D005260:Female; D006333:Heart Failure / Q000097:blood* / Q000401:mortality* / Q000503:physiopathology; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism*; D011237:Predictive Value of Tests; D011379:Prognosis; D012016:Reference Values; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D016019:Survival Analysis
chemical_list: D015415:Biomarkers; C117400:C1D protein, human; D056970:Co-Repressor Proteins
keywords: DNA; innate immunity; mitochondria; toll-like receptor 9