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

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 inflammat...

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Autores principales:	Masahiro Yamazoe, Tetsuo Sasano, Kensuke Ihara, Kentaro Takahashi, Wakana Nakamura, Naomi Takahashi, Hiroaki Komuro, Satomi Hamada, Tetsushi Furukawa
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/dc2b3b0c509c46918edf0a33c32ae542
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spelling	oai:doaj.org-article:dc2b3b0c509c46918edf0a33c32ae5422021-12-02T17:05:11ZSparsely methylated mitochondrial cell free DNA released from cardiomyocytes contributes to systemic inflammatory response accompanied by atrial fibrillation10.1038/s41598-021-85204-72045-2322https://doaj.org/article/dc2b3b0c509c46918edf0a33c32ae5422021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-85204-7https://doaj.org/toc/2045-2322Abstract 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.Masahiro YamazoeTetsuo SasanoKensuke IharaKentaro TakahashiWakana NakamuraNaomi TakahashiHiroaki KomuroSatomi HamadaTetsushi FurukawaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Masahiro Yamazoe Tetsuo Sasano Kensuke Ihara Kentaro Takahashi Wakana Nakamura Naomi Takahashi Hiroaki Komuro Satomi Hamada Tetsushi Furukawa Sparsely methylated mitochondrial cell free DNA released from cardiomyocytes contributes to systemic inflammatory response accompanied by atrial fibrillation
description	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.
format	article
author	Masahiro Yamazoe Tetsuo Sasano Kensuke Ihara Kentaro Takahashi Wakana Nakamura Naomi Takahashi Hiroaki Komuro Satomi Hamada Tetsushi Furukawa
author_facet	Masahiro Yamazoe Tetsuo Sasano Kensuke Ihara Kentaro Takahashi Wakana Nakamura Naomi Takahashi Hiroaki Komuro Satomi Hamada Tetsushi Furukawa
author_sort	Masahiro Yamazoe
title	Sparsely methylated mitochondrial cell free DNA released from cardiomyocytes contributes to systemic inflammatory response accompanied by atrial fibrillation
title_short	Sparsely methylated mitochondrial cell free DNA released from cardiomyocytes contributes to systemic inflammatory response accompanied by atrial fibrillation
title_full	Sparsely methylated mitochondrial cell free DNA released from cardiomyocytes contributes to systemic inflammatory response accompanied by atrial fibrillation
title_fullStr	Sparsely methylated mitochondrial cell free DNA released from cardiomyocytes contributes to systemic inflammatory response accompanied by atrial fibrillation
title_full_unstemmed	Sparsely methylated mitochondrial cell free DNA released from cardiomyocytes contributes to systemic inflammatory response accompanied by atrial fibrillation
title_sort	sparsely methylated mitochondrial cell free dna released from cardiomyocytes contributes to systemic inflammatory response accompanied by atrial fibrillation
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/dc2b3b0c509c46918edf0a33c32ae542
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Sparsely methylated mitochondrial cell free DNA released from cardiomyocytes contributes to systemic inflammatory response accompanied by atrial fibrillation

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