Leukocyte Mitochondrial DNA Copy Number Is Associated with Chronic Obstructive Pulmonary Disease

Liu, Shih-Feng; Kuo, Ho‐Chang; Tseng, Chun-Chieh; Huang, Hung‐Tsai; Chen, Yung‐Che; Lin, Meng‐Chih

doi:10.1371/journal.pone.0138716

Cited by 35 publications

(28 citation statements)

References 35 publications

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“…In at least 1 study, exogenous mtDNA given intravascularly to rodents did not increase circulating mtDNA but increased u-mtDNA (26). U-mtDNA may also originate from renal cells, including glomerular or tubular epithelial cells (56), endothelial cells (44), and immune cells (6,12), as well as lung-derived cell sources (5)(6)(7)(8)(9)(10)(11)16) or muscle (65); further mechanistic studies are needed to identify the source of extracellular mtDNA in COPD. Whether u-mtDNA in COPD is a marker of disease or is pathogenic in itself remains to be determined.…”

Section: L I N I C a L M E D I C I N Ementioning

confidence: 99%

“…One underlying biological mechanism that may provide insight into COPD pathogenesis and progression is mitochondrial dysfunction, which is consistently observed in cells derived from COPD subjects (5)(6)(7)(8)(9)(10)(11)(12)(13), as well as in experimental COPD models (11,14). Such mitochondrial dysfunction is associated with the leakage of mitochondrial DNA (mtDNA) (15)(16)(17)(18)(19), a mitochondrial derived danger-associated molecular pattern (mtDAMP) (20,21).…”

Section: Introductionmentioning

confidence: 99%

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Association of urine mitochondrial DNA with clinical measures of COPD in the SPIROMICS cohort

Zhang¹,

Rice²,

Hoffman³

et al. 2020

JCI Insight

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BACKGROUND. Mitochondrial dysfunction, a proposed mechanism of chronic obstructive pulmonary disease (COPD) pathogenesis, is associated with the leakage of mitochondrial DNA (mtDNA), which may be detected extracellularly in various bodily fluids. Despite evidence for the increased prevalence of chronic kidney disease in COPD subjects and for mitochondrial dysfunction in the kidneys of murine COPD models, whether urine mtDNA (u-mtDNA) associates with measures of disease severity in COPD is unknown. METHODS. Cell-free u-mtDNA, defined as copy number of mitochondrially encoded NADH dehydrogenase-1 (MTND1) gene, was measured by quantitative PCR and normalized to urine creatinine in cell-free urine samples from participants in the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS) cohort. Urine albumin/creatinine ratios (UACR) were measured in the same samples. Associations between u-mtDNA, UACR, and clinical disease parameters-including FEV 1 % predicted, clinical measures of exercise tolerance, respiratory symptom burden, and chest CT measures of lung structure-were examined. RESULTS. U-mtDNA and UACR levels were measured in never smokers (n = 64), smokers without airflow obstruction (n = 109), participants with mild/moderate COPD (n = 142), and participants with severe COPD (n = 168). U-mtDNA was associated with increased respiratory symptom burden, especially among smokers without COPD. Significant sex differences in u-mtDNA levels were observed, with females having higher u-mtDNA levels across all study subgroups. U-mtDNA associated with worse spirometry and CT emphysema in males only and with worse respiratory symptoms in females only. Similar associations were not found with UACR.

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Section: L I N I C a L M E D I C I N Ementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Association of urine mitochondrial DNA with clinical measures of COPD in the SPIROMICS cohort

Zhang¹,

Rice²,

Hoffman³

et al. 2020

JCI Insight

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“…Although mtDNA copy numbers were not specifically assessed, the expression of mtDNA‐encoded COX2 was reduced, hinting to a reduction of mtDNA copy numbers. Accordingly, in patients with chronic obstructive pulmonary disease, a disorder associated with oxidative stress, leukocyte mtDNA copy numbers were lower than in healthy controls (Liu et al , ).…”

Section: Effects Of Reactive Oxygen Species On Epigenetic Mechanismsmentioning

confidence: 99%

The epigenetic landscape related to reactive oxygen species formation in the cardiovascular system

Kietzmann

Petry

Shvetsova

et al. 2017

British J Pharmacology

189

119

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*Authors contributed equally.Cardiovascular diseases are among the leading causes of death worldwide. Reactive oxygen species (ROS) can act as damaging molecules but also represent central hubs in cellular signalling networks. Increasing evidence indicates that ROS play an important role in the pathogenesis of cardiovascular diseases, although the underlying mechanisms and consequences of pathophysiologically elevated ROS in the cardiovascular system are still not completely resolved. More recently, alterations of the epigenetic landscape, which can affect DNA methylation, post-translational histone modifications, ATP-dependent alterations to chromatin and non-coding RNA transcripts, have been considered to be of increasing importance in the pathogenesis of cardiovascular diseases. While it has long been accepted that epigenetic changes are imprinted during development or even inherited and are not changed after reaching the lineage-specific expression profile, it becomes more and more clear that epigenetic modifications are highly dynamic. Thus, they might provide an important link between the actions of ROS and cardiovascular diseases. This review will provide an overview of the role of ROS in modulating the epigenetic landscape in the context of the cardiovascular system. This article is part of a themed section on Redox Biology and Oxidative Stress in Health and Disease. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.12/issuetoc Abbreviations 5hmC, 5-hydroxymethylcytosine; 5mC, 5-methylcytosine; 8-oxodG, 8-oxo-2 0 -deoxyguanosine; BAF, Brg1-associated factors; BER, base excision repair; BRG1, Brahma-related gene 1; BRM, Brahma; CBP, CREB binding protein; CHD, chromodomain helicase DNA-binding; CK2, casein kinase 2; CpG, 5-C-phosphate-G-3 0 ; Cys, cysteine; DNMT, DNA methyltransferase; DPF3a, double plant homeodomain (PHD) finger protein 3a; E2F1, E2F transcription factor 1; ETC, electron transport chain; EZH2, enhancer of zeste 2 PRC2 subunit; GCN5, general control nonderepressible 5; GPX1, glutathione peroxidase; HAT, histone acetyltransferases; HDAC, histone deacetylase; HDM, histone demethylase; HIF1, hypoxia-inducible factor 1; HMT, histone methyltransferases; ISWI, imitation switch; KDM, histone demethylase; LINE-1, long interspersed nuclear element-1; lncRNA, long non-coding RNA; LSD1, lysine demethylase 1A; miRNA, microRNA; mtDNA, mitochondrial DNA; nDNA, nuclear DNA; NOX, NADPH oxidases; OGG1, 8-oxoguanine DNA glycosylase; OXPHOS, oxidative phosphorylation; PARP, poly(ADP-ribose)-polymerase; PGC-1α, peroxisome proliferator-activated receptor gamma coactivator 1-alpha; PHD, prolyl hydroxylase; PolG, polymerase γ; PPARγ, peroxisome proliferator-activated receptor gamma; PRC, polycomb repressive complex; PRMT, protein arginine N-methyltransferase; ROS, reactive oxygen species; SAM, S-adenosyl methionine; SET, Su(var)3-9, Enhancer of Zeste, Trithorax; SIRT, sirtuin; SMYD1, SET and MYND domain-containing protein 1; SNF2H, sucrose nonfermentable 2 hom...

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“…AECOPD and PE are associated with a wide range of inflammatory cells, mediators and cytokine network components, including P-selectin (11,12), inflammatory cytokines (13,14) and leucocytes (15,16). Previous studies have indicated that eosinophilic airway inflammation is also associated with the development of severe AECOPD (17)(18)(19).…”

Section: Introductionmentioning

confidence: 99%

Eosinophilic biomarkers for detection of acute exacerbation of chronic obstructive pulmonary disease with or without pulmonary embolism

Yang

Lü

Shu

et al. 2017

Experimental and Therapeutic Medicine

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Abstract. Eosinophilia has been implicated in the pathophysiology of acute exacerbation of chronic obstructive pulmonary disease (AECOPD). However, the role of eosinophil activation in the development of AECOPD remains unclear. In the present study, the reliability of plasma levels of eosinophil activation markers, including eosinophil cationic protein (ECP), major basic protein (MBP), eosinophil-derived neurotoxin (EDN) and eosinophil peroxidase (EPX), were measured and used as diagnostic biomarkers of AECOPD with or without pulmonary embolism (PE). A total of 47 patients with AECOPD, 30 patients with AECOPD/PE and 35 healthy adults were enrolled in the present study. Plasma levels of ECP, EDN, EPX and MBP were measured using commercial ELISA kits. The mean concentrations of plasma ECP, EDN, EPX and MBP in the patients with AECOPD was significantly 2.87-, 3.06-, 1.60-and 1.92-fold higher, respectively, compared with the control group (P<0.05). Similar results were obtained in patients with AECOPD/PE, for whom plasma levels of ECP, EDN, EPX and MBP were significantly 2.06-, 2.21-, 1.42-and 2.42-fold higher, respectively, compared with the controls (P<0.05). No significant differences were observed in the levels of these proteins between patients with AECOPD or AECOPD/PE. Among the four potential markers, ECP was determined to be the optimal marker for distinguishing patients with AECOPD or AECOPD/PE from the controls. No significant correlation was observed between marker concentrations and gender, age or disease severity. The results of the present study may have clinical applications in the diagnosis of AECOPD using these novel biomarkers.

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Leukocyte Mitochondrial DNA Copy Number Is Associated with Chronic Obstructive Pulmonary Disease

Cited by 35 publications

References 35 publications

Association of urine mitochondrial DNA with clinical measures of COPD in the SPIROMICS cohort

Association of urine mitochondrial DNA with clinical measures of COPD in the SPIROMICS cohort

The epigenetic landscape related to reactive oxygen species formation in the cardiovascular system

Eosinophilic biomarkers for detection of acute exacerbation of chronic obstructive pulmonary disease with or without pulmonary embolism

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