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

Yangchen Dhondup; Thor Ueland; Christen Peder Dahl; Erik Tandberg Askevold; Øystein Sandanger; Arnt Fiane; Ingrid Kristine Ohm; Ivar Sjaastad; Alexandra Vanessa Finsen; Anne Wæhre; Lars Gullestad; Pål Aukrust; Arne Yndestad; Leif Erik Vinge

doi:10.1016/j.cardfail.2016.06.013

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

J Card Fail. 2016 Oct;22(10):823-8. doi: 10.1016/j.cardfail.2016.06.013. Epub 2016 Jun 24.

Authors

Affiliations

¹ 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.
² Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway; Faculty of Medicine, University of Oslo, Norway.
³ 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.
⁴ Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway; Center for Heart failure Research, University of Oslo, Oslo, Norway.
⁵ 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.
⁶ Faculty of Medicine, University of Oslo, Norway; Department of Cardiothoracic Surgery, Oslo University Hospital Rikshospitalet, Oslo, Norway.
⁷ 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.
⁸ Center for Heart failure Research, University of Oslo, Oslo, Norway; Institute for Experimental Research, Oslo University Hospital, Ullevål, Oslo, Norway.
⁹ 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.
¹⁰ 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.
¹¹ 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.

PMID: 27349571
DOI: 10.1016/j.cardfail.2016.06.013

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).

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.

Keywords: DNA; innate immunity; mitochondria; toll-like receptor 9.

MeSH terms

Aged
Biomarkers / blood
Case-Control Studies
Co-Repressor Proteins / metabolism*
Female
Heart Failure / blood*
Heart Failure / mortality*
Heart Failure / physiopathology
Humans
Kaplan-Meier Estimate
Male
Middle Aged
Mitochondria / metabolism*
Predictive Value of Tests
Prognosis
Reference Values
Severity of Illness Index
Statistics, Nonparametric
Survival Analysis

Substances

Biomarkers
C1D protein, human
Co-Repressor Proteins