Evidence map›Paper›PMID 33737532›Full record

ArticleScientific reports2021

Sparsely methylated mitochondrial cell free DNA released from cardiomyocytes contributes to systemic inflammatory response accompanied by atrial fibrillation.

Masahiro Yamazoe, Tetsuo Sasano, Kensuke Ihara, Kentaro Takahashi, Wakana Nakamura, Naomi Takahashi, Hiroaki Komuro, Satomi Hamada, Tetsushi Furukawa

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
1.5field-weighted citation impact, top 20% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

17 citing papers in PubMed, 27 citations in OpenAlex.

  1. Review
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  4. Mitochondrial DNA signals driving immune responses: Why, How, Where?Cell communication and signaling : CCS · 2025
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 1 country.

Masahiro YamazoeDepartment of Bio-Informational Pharmacology, Medical Research Institute, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.
Tetsuo SasanoDepartment of Cardiovascular Physiology, Tokyo Medical and Dental University (TMDU), Tokyo, Japan. sasano.cvm@tmd.ac.jp.
Kensuke IharaDepartment of Bio-Informational Pharmacology, Medical Research Institute, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.
Kentaro TakahashiDepartment of Bio-Informational Pharmacology, Medical Research Institute, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.
Wakana NakamuraDepartment of Cardiovascular Physiology, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.
Naomi TakahashiDepartment of Cardiovascular Physiology, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.
Hiroaki KomuroDepartment of Cardiovascular Physiology, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.
Satomi HamadaDepartment of Cardiovascular Physiology, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.
Tetsushi FurukawaDepartment of Bio-Informational Pharmacology, Medical Research Institute, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.
The University of Tokyo · JPTokyo Medical and Dental University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Systemic inflammation is assumed to be the consequence and the cause of atrial fibrillation (AF); however, the underlying mechanism remains unclear. We aimed to evaluate the level of cell-free DNA (cfDNA) in patients with AF and AF mimicking models, and to illuminate its impact on inflammation. Peripheral blood was obtained from 54 patients with AF and 104 non-AF controls, and cfDNA was extracted. We extracted total cfDNA from conditioned medium after rapid pacing to HL-1 cells. Nuclear and mitochondrial DNA were separately extracted and fragmented to simulate nuclear-cfDNA (n-cfDNA) and mitochondrial-cfDNA (mt-cfDNA). The AF group showed higher cfDNA concentration than the non-AF group (12.6 [9.0-17.1] vs. 8.1 [5.3-10.8] [ng/mL], p < 0.001). The copy numbers of n-cfDNA and mt-cfDNA were higher in AF groups than in non-AF groups; the difference of mt-cfDNA was particularly apparent (p = 0.011 and p < 0.001, respectively). Administration of total cfDNA and mt-cfDNA to macrophages significantly promoted IL-1β and IL-6 expression through TLR9, whereas n-cfDNA did not. Induction of cytokine expression by methylated mt-cfDNA was lower than that by unmethylated mt-cfDNA. Collectively, AF was associated with an increased cfDNA level, especially mt-cfDNA. Sparsely methylated mt-cfDNA released from cardiomyocytes may be involved in sterile systemic inflammation accompanied by AF.

Indexed as

AdultAgedAnimalsAtrial FibrillationBiomarkersCell-Free Nucleic AcidsDisease Models, AnimalDisease ProgressionDNA MethylationDNA, MitochondrialFemaleHumansIncidenceInflammationInterleukin-1betaInterleukin-6BiomarkersCell-Free Nucleic AcidsDNA, MitochondrialInterleukin-1betaInterleukin-6Toll-Like Receptor 9

Identifiers

PMID33737532
PMCPMC7973420
OpenAlexW3137563064

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.