Low Circulating Levels of Mitochondrial and High Levels of Nuclear DNA Predict Mortality in Chronic Heart Failure

JOURNAL OF CARDIAC FAILURE

卷:22

Article

Dhondup, Yangchen^1,2,3,4  Ueland, Thor^1,4  Dahl, Christen Peder^1,2,5  Askevold, Erik Tandberg^1,2  Sandanger, Oystein^1,2,3,4  Fiane, Arnt^4,6  Ohm, Ingrid Kristine^1,2,3  Sjaastad, Ivar^2,7  Finsen, Alexandra Vanessa^1,2,3  Waehre, Anne^2,7  Gullestad, Lars^2,4,5,8  Aukrust, Pal^1,3,9  Yndestad, Arne^1,2,3,4  Vinge, Leif Erik^1,2,5,10 

[1] Oslo Univ Hosp, Rikshosp, Internal Med Res Inst, Postbox 4950 Nydalen, N-0424 Oslo, Norway

[2] Univ Oslo, Ctr Heart Failure Res, Oslo, Norway

[3] Univ Oslo, KG Jebsen Inflammat Res Ctr, Oslo, Norway

[4] Univ Oslo, Fac Med, N-0316 Oslo, Norway

[5] Oslo Univ Hosp, Rikshosp, Dept Cardiol, Oslo, Norway

[6] Oslo Univ Hosp, Rikshosp, Dept Cardiothorac Surg, Oslo, Norway

[7] Oslo Univ Hosp, Inst Expt Res, Oslo, Norway

[8] Univ Oslo, KG Jebsen Cardiovasc Res Ctr, Oslo, Norway

[9] Oslo Univ Hosp, Rikshosp, Sect Clin Immunol & Infect Dis, Oslo, Norway

[10] Diakonhjemmet Hosp, Dept Internal Med, Oslo, Norway

关键词: DNA;    innate immunity;    mitochondria;    toll-like receptor 9;   

DOI  :  10.1016/j.cardfail.2016.06.013

来源: Elsevier

【 摘 要 】

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). Methods and 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.

【 授权许可】

Free