Level of blood cell-free circulating mitochondrial DNA as a novel biomarker of acute myocardial ischemia

Судаков, Н. П.; Popkova, Tatyana; Катышев, А. И.; Гольдберг, О. А.; Никифоров, С. Б.; Pushkarev, B. G.; Клименков, И. В.; Лепехова, Светлана Александровна; Апарцин, К. А.; Nevinsky, Georgy A.; Konstantinov, Yu. M.

doi:10.1134/s000629791510020x

Cited by 19 publications

(14 citation statements)

References 32 publications

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“…It was already explored the dynamics of the level of free circulating blood plasma mtDNA in acute myocardial ischemia and observed the increase in blood plasma mtDNA concentration [5–7]. Recently, we found the raise of concentration of free circulating mitochondrial DNA in blood after injection of adrenaline that caused the development of multiple small focal myocardial ischemia in Wistar rats [8, 9]. Recent observations [10] reveal the molecular mechanism behind the development of acute heart failure in animal models, where mitochondrial DNA is an important pathogenic factor.…”

Section: Introductionmentioning

confidence: 99%

The level of free circulating mitochondrial DNA in blood as predictor of death in case of acute coronary syndrome

et al. 2017

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BackgroundThe efficacy of treating acute myocardial ischemic damages depends, to a large extent, on the development of technologies for predicting their course and outcome. The aim of this paper was to explore whether it would be possible to consider the content of free circulating mitochondrial DNA as a danger-associated molecular pattern for assessing the probability of death from myocardial infarction.MethodsWe have analyzed the clinical outcomes based on discharge summaries and autopsy reports obtained in the course of the PROTOCOL observational trial. This study was approved by the Irkutsk Scientific Center of Surgery and Traumatology ethics committee (protocol No. 3, 10.08.2015). To examine whether the assessment of the level of free circulating mtDNA in acute coronary syndrome can help predicting clinical outcomes, all patients were divided into two groups: group 1, involving those who survived during 30 days after hospitalization, and group 2, involving those who died during this time. A quantitative analysis of the free circulating mtDNA was conducted using the PCR method in situ.ResultsThe analysis showed that in patients who survived the level of freely circulating mtDNA (36.0 copies/ml) was 164 times lower than in those who died (5900 copies/ml, p = 0.049). It should be mentioned that according to the logistic regression analysis, the probability of death of patients with the increased level of blood plasma mtDNA (more than 4000 copies/ml) is 50%.ConclusionsThus, the PROTOCOL observational trial proved that the increase in the content of free circulating mtDNA in blood is a predictor of lethal outcome in patients with acute coronary syndrome. Trial registration The observational studies (those in which the assignment of the medical intervention is not at the discretion of the investigator) do not require registration.

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Section: Introductionmentioning

confidence: 99%

The level of free circulating mitochondrial DNA in blood as predictor of death in case of acute coronary syndrome

et al. 2017

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“…The identification of circulating cell-free mitochondrial DNA (ccf-mtDNA) in 2000 [1], prompted a wave of studies assessing the utility of ccf-mtDNA as a biomarker of disease [2][3][4][5][6][7], detection of cancers [8][9][10][11][12] and susceptibility to comorbidities during HIV infection [13,14].…”

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confidence: 99%

Circulating cell-free mitochondrial DNA levels in Parkinson’s disease are influenced by treatment

Lowes

Pyle

Santibanez‐Koref

et al. 2020

Mol Neurodegeneration

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Several studies have linked circulating cell-free mitochondrial DNA (ccf-mtDNA) to human disease. In particular, reduced ccf-mtDNA levels in the cerebrospinal fluid (CSF) of both Alzheimer's and Parkinson's disease (PD) patients have raised the hypothesis that ccf-mtDNA could be used as a biomarker for neurodegenerative disease onset and progression. However, how a reduction of CSF ccf-mtDNA levels relates to neurodegeneration remains unclear. Many factors are likely to influence ccf-mtDNA levels, such as concomitant therapeutic treatment and comorbidities. In this study we aimed to investigate these factors, quantifying CSF ccf-mtDNA from the Parkinson's Progression Markers Initiative in 372 PD patients and 159 matched controls at two time points. We found that ccf-mtDNA levels appear significantly reduced in PD cases when compared to matched controls and are associated with cognitive impairment. However, our data indicate that this reduction in ccf-mtDNA is also associated with the commencement, type and duration of treatment. Additionally, we found that ccf-mtDNA levels are associated with comorbidities such as depression and insomnia, however this was only significant if measured in the absence of treatment. We conclude that in PD, similar to reports in HIV and sepsis, comorbidities and treatment can both influence ccf-mtDNA homeostasis, raising the possibility that ccf-mtDNA may be useful as a biomarker for treatment response or the development of secondary phenotypes. Given that, clinically, PD manifests often decades after neurodegeneration begins, predicting who will develop disease is important. Also, identifying patients who will respond to existing treatments or develop secondary phenotypes will have increased clinical importance as PD incidence rises.

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“…Mitochondrial DNA activates p38 mitogen-activated protein kinase (MAPK) by TLR9 with leakage of matrix metalloproteinase 8 and 9 in neutrophils [36]. Later, another study observed the increase of MMP9 and phosphorylated p38 in response to mitochondrial DNA treatment of neutrophils [37]. In addition, Wei et al [30] also noted similar observation: pretreatment with ODN2088 (a TLR9 inhibitor) prevented p38 MAPK pathway activation and MMP8 leakage.…”

Section: Mitochondrial Dna and Toll-like Receptormentioning

confidence: 80%

Mitochondrial DNA: A Key Regulator of Anti-Microbial Innate Immunity

Kausar

Yang

Abbas

et al. 2020

Genes

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During the last few years, mitochondrial DNA has attained much attention as a modulator of immune responses. Due to common evolutionary origin, mitochondrial DNA shares various characteristic features with DNA of bacteria, as it consists of a remarkable number of unmethylated DNA as 2′-deoxyribose cytidine-phosphate-guanosine (CpG) islands. Due to this particular feature, mitochondrial DNA seems to be recognized as a pathogen-associated molecular pattern by the innate immune system. Under the normal physiological situation, mitochondrial DNA is enclosed in the double membrane structure of mitochondria. However, upon pathological conditions, it is usually released into the cytoplasm. Growing evidence suggests that this cytosolic mitochondrial DNA induces various innate immune signaling pathways involving NLRP3, toll-like receptor 9, and stimulator of interferon genes (STING) signaling, which participate in triggering downstream cascade and stimulating to produce effector molecules. Mitochondrial DNA is responsible for inflammatory diseases after stress and cellular damage. In addition, it is also involved in the anti-viral and anti-bacterial innate immunity. Thus, instead of entire mitochondrial importance in cellular metabolism and energy production, mitochondrial DNA seems to be essential in triggering innate anti-microbial immunity. Here, we describe existing knowledge on the involvement of mitochondrial DNA in the anti-microbial immunity by modulating the various immune signaling pathways.

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Level of blood cell-free circulating mitochondrial DNA as a novel biomarker of acute myocardial ischemia

Cited by 19 publications

References 32 publications

The level of free circulating mitochondrial DNA in blood as predictor of death in case of acute coronary syndrome

The level of free circulating mitochondrial DNA in blood as predictor of death in case of acute coronary syndrome

Circulating cell-free mitochondrial DNA levels in Parkinson’s disease are influenced by treatment

Mitochondrial DNA: A Key Regulator of Anti-Microbial Innate Immunity

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