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

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• 作者：Yangchen Dhondup ; MD¹ ; ² ; ³ ; ⁴ ; ^{yangched@gmail.com" class="auth_mail" title="E-mail the corresponding author} ; Thor Ueland ; PhD¹ ; ⁴ ; Christen Peder Dahl ; MD ; PhD¹ ; ² ; ⁵ ; Erik Tandberg Askevold ; MD ; PhD¹ ; ² ; Ø ; ystein Sandanger ; MD ; PhD¹ ; ² ; ³ ; ⁴ ; Arnt Fiane ; MD ; PhD⁴ ; ⁶ ; Ingrid Kristine Ohm ; PhD¹ ; ² ; ³ ; Ivar Sjaastad ; MD ; PhD² ; ⁷ ; Alexandra Vanessa Finsen ; MD ; PhD¹ ; ² ; ³ ; Anne Wæ ; hre ; MD ; PhD² ; ⁷ ; Lars Gullestad ; MD ; PhD² ; ⁴ ; ⁵ ; ⁸ ; På ; l Aukrust ; MD ; PhD¹ ; ³ ; ⁴ ; ⁹ ; Arne Yndestad ; MScPharm ; PhD¹ ; ² ; ³ ; ⁴ ; ^&dagger ; ; Leif Erik Vinge ; MD ; PhD¹ ; ² ; ⁵ ; ¹⁰ ; ^&dagger ;
• 关键词：DNA ; innate immunity ; mitochondria ; toll-like receptor 9
• 刊名：Journal of Cardiac Failure
• 出版年：2016
• 出版时间：October 2016
• 年：2016
• 卷：22
• 期：10
• 页码：823-828
• 全文大小：547 K

文摘

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.