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European Journal of Medical Research
Published in: European Journal of Medical Research 1/2017

Open Access 01-12-2017 | Research

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

Authors: Nikolay P. Sudakov, Konstantin A. Apartsin, Svetlana A. Lepekhova, Sergey B. Nikiforov, Alexander I. Katyshev, Galina I. Lifshits, Anna V. Vybivantseva, Yuri M. Konstantinov

Published in: European Journal of Medical Research | Issue 1/2017

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Abstract

Background

The 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.

Methods

We 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.

Results

The 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%.

Conclusions

Thus, 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.
Literature
1.
Zhang Q, Raoof M, Chen Y, Sumi Y, Sursal T, Junger W, Brohi K, Itagaki K, Hauser CJ. Circulating mitochondrial DAMPs cause inflammatory responses to injury. Nature. 2010;464:104–7.CrossRefPubMedPubMedCentral
2.
Ellinger J, Müller SC, Wernert N, von Ruecker A, Bastian PJ. Mitochondrial DNA in serum of patients with prostate cancer: a predictor of biochemical recurrence after prostatectomy. BJU Int. 2008;102:628–32.CrossRefPubMed
3.
Nakahira K, Kyung SY, Rogers AJ, Gazourian L, Youn S, Massaro AF, Quintana C, Osorio JC, Wang Z, Zhao Y, Lawler LA, Christie JD, Meyer NJ, Mc Causland FR, Waikar SS, Waxman AB, Chung RT, Bueno R, Rosas IO, Fredenburgh LE, Baron RM, Christiani DC, Hunninghake GM, Choi AM. Circulating mitochondrial DNA in patients in the ICU as a marker of mortality: derivation and validation. PLoS Med. 2013;10:e1001577.CrossRefPubMedPubMedCentral
4.
Arnalich F, Maldifassi MC, Ciria E, Codoceo R, Renart J, Fernández-Capitán C, Herruzo R, Garcia-Rio F, López-Collazo E, Montiel C. Plasma levels of mitochondrial and nuclear DNA in patients with massive pulmonary embolism in the emergency department: a prospective cohort study. Crit Care. 2013;17:R90.CrossRefPubMedPubMedCentral
5.
Wang L, Xie L, Zhang Q, Cai X, Tang Y, Wang L, Hang T, Liu J, Gong J. Plasma nuclear and mitochondrial DNA levels in acute myocardial infarction patients. Coron Artery Dis. 2015;26:296–300.CrossRefPubMedPubMedCentral
6.
Bliksoen M, Mariero LH, Ohm IK, Haugen F, Yndestad A, Solheim S, Seljeflot I, Ranheim T, Andersen GO, Aukrust P, Valen G, Vinge LE. Increased circulating mitochondrial DNA after myocardial infarction. Int J Cardiol. 2012;158:132–4.CrossRefPubMed
7.
Arnalich F, Codoceo R, López-Collazo E, Montiel C. Circulating cell-free mitochondrial DNA: a better early prognostic marker in patients with out-of-hospital cardiac arrest. Resuscitation. 2012;83:e162–3.CrossRefPubMed
8.
Sudakov NP, Popkova TP, Novikova MA, Katyshev AV, Nikiforov SB, Pushkarev BG, Goldberg OA, Klimenkov IV, Lepekhova SA, Ezhikeeva SD, Ten MN, Osipov VG, Konstantinov YM. The level of blood plasma mitochondrial DNA upon acute myocardium damage in experiment. Biopolym Cell. 2012;28:321–4.CrossRef
9.
Sudakov NP, Popkova TP, Katyshev AI, Goldberg OA, Nikiforov SB, Pushkarev BG, Klimenkov IV, Lepekhova SA, Apartsin KA, Nevinsky GA, Konstantinov YM. Level of blood cell-free circulating mitochondrial DNA as a novel biomarker of acute myocardial ischemia. Biochemistry (Moscow). 2015;80(10):1387–92.CrossRef
10.
Oka T, Hikoso S, Yamaguchi O, Taneike M, Takeda T, Tamai T, Oyaba J, Murakawa T, Nakayama H, Nishida K, Akira S, Yamamoto A, Komuro I, Otsu K. Mitochondrial DNA that escapes from autophagy causes inflammation and heart failure. Nature. 2012;485:251–5.CrossRefPubMedPubMedCentral
11.
Lifshits GI, Apartsin KA. PROTOCOL (Personalized therapy with clopidogrel during coronary stent implantation for acute coronary syndrome taking into account genetic polymorphism) prospective multicenter observational study. Qual Clin Pract. 2015;1:78–87.
12.
CURRENT-OASIS 7 Investigators, Mehta SR, Bassand JP, Chrolavicius S, Diaz R, Eikelboom JW, Fox KA, Granger CB, Jolly S, Joyner CD, Rupprecht HJ, Widimsky P, Afzal R, Pogue J, Yusuf S. Dose comparisons of clopidogrel and aspirin in acute coronary syndromes. N Engl J Med. 2010;363(10):930–42.CrossRef
13.
Cutlip DE, Windecker S, Mehran R, Boam A, Cohen DJ, van Es G-A, Steg PG, Morel M-A, Mauri L, Vranckx P, McFadden E, Lansky A, Hamon M, Krucoff MW, Serruys PW. Clinical end points in coronary stent trials a case for standardized definitions. Circulation. 2007;115:2344–51.CrossRefPubMed
14.
Itagaki K, Kaczmarek E, Lee YT, Tang IT, Isal B, Adibnia Y, Sandker N, Grimm MJ, Segal BH, Otterbein E, Hauser CJ. Mitochondrial DNA released by trauma induces neutrophil extracellular traps. PLoS ONE. 2015;10(3):e0120549.CrossRefPubMedPubMedCentral
15.
Knez J, Winckelmans E, Plusquin M, Thijs L, Cauwenberghs N, Staessen JA, Nawrot T, Kuznetsova T. Correlates of peripheral blood mitochondrial DNA copy number in a general population. J Hypertens. 2015;33(1):e2.CrossRefPubMed
16.
Knez J, Winckelmans E, Plusquin M, Thijs L, Cauwenberghs N, Gu Y, Staessen JA, Nawrot TS, Kuznetsova T. Correlates of peripheral blood mitochondrial DNA content in a general population. Am J Epidemiol. 2016;183(2):138–46.PubMed
17.
Gahan PB. Biology of circulating nucleic acids and possible roles in diagnosis and treatment in diabetes and cancer. Infect Disord Drug Targets. 2012;12:360–70.CrossRefPubMed
18.
Koulintchenko M, Temperley RJ, Mason PA, Dietrich A, Lightowlers RN. Natural competence of mammalian mitochondria allows the molecular investigation of mitochondrial gene expression. Hum Mol Genet J. 2006;15:143–54.CrossRef
19.
Klimenko ES, Mileiko VA, Morozkin ES, Laktionov PP, Konstantinov YM. Study of DNA import and export in potato (Solanum tuberosum) mitochondria using quantitative PCR. Biochem (Moscow) Suppl Ser: Membr Cell Biol. 2011;5(2):170–6.CrossRef
20.
Guescini M, Guidolin D, Vallorani L, Casadei L, Gioacchini AM, Tibollo P, Battistelli M, Falcieri E, Battistin L, Agnati LF, Stocchi V. C2C12 myoblasts release micro-vesicles containing mtDNA and proteins involved in signal transduction. Exp Cell Res. 2010;316:1977–84.CrossRefPubMed
21.
Zhang Q, Itagaki K, Hauser CJ. Mitochondrial DNA is released by shock and activates neutrophils via p38 map kinase. Shock. 2010;34:55–9.CrossRefPubMed
22.
Yousefi S, Mihalache C, Kozlowski E, Schmid I, Simon HU. Viable neutrophils release mitochondrial DNA to form neutrophil extracellular traps. Cell Death Differ. 2009;16:1438–44.CrossRefPubMed
23.
Kireeva VV, Koch NV, Lifshits GI, Apartsin KA. Endothelial dysfunction as cornerstone of cardiovascular events: molecular and pharmaceutic aspects. Rus J Cardiol. 2014;10:64–8.
Metadata
Title
The level of free circulating mitochondrial DNA in blood as predictor of death in case of acute coronary syndrome
Authors
Nikolay P. Sudakov
Konstantin A. Apartsin
Svetlana A. Lepekhova
Sergey B. Nikiforov
Alexander I. Katyshev
Galina I. Lifshits
Anna V. Vybivantseva
Yuri M. Konstantinov
Publication date
01-12-2017
Publisher
BioMed Central
Published in
European Journal of Medical Research / Issue 1/2017
Electronic ISSN: 2047-783X
DOI
https://doi.org/10.1186/s40001-016-0241-x

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