Mitochondrial DNA Together with miR-142-3p in Plasma Can Predict Unfavorable Outcomes in Patients after Acute Myocardial Infarction

被引:15
作者
Barbalata, Teodora [1 ]
Scarlatescu, Alina, I [2 ,3 ]
Sanda, Gabriela M. [1 ]
Toma, Laura [1 ]
Stancu, Camelia S. [1 ]
Dorobantu, Maria [2 ,3 ]
Micheu, Miruna M. [3 ]
Sima, Anca, V [1 ]
Niculescu, Loredan S. [1 ]
机构
[1] Romanian Acad, Lipid Dept, Inst Cellular Biol & Pathol Nicolae Simionescu, 8 BP Hasdeu St, Bucharest 050568, Romania
[2] Carol Davila Univ Med & Pharm, Dept Cardiol, Bucharest 050474, Romania
[3] Clin Emergency Hosp Bucharest, Dept Cardiol, Bucharest 014461, Romania
关键词
biomarker; cardiovascular disease; cell-free DNA; microRNA; mitochondrial DNA; myocardial infarction; CELL-FREE DNA; COPY-NUMBER; PROGNOSTIC VALUE; ASSOCIATION;
D O I
10.3390/ijms23179947
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Myocardial infarction is one of the leading causes of death worldwide, despite numerous efforts to find efficient prognostic biomarkers and treatment targets. In the present study, we aimed to assess the potential of six microRNAs known to be involved in cardiovascular diseases, cell-free DNA (cfDNA), and mitochondrial DNA (mtDNA) circulating in plasma to be used as prognostic tools for the occurrence of unfavorable outcomes such as major adverse cardiovascular events (MACE) after acute ST-segment elevation myocardial infarction (STEMI). Fifty STEMI patients were enrolled and monitored for 6 months for the occurrence of MACE. Plasma was collected at three time points: upon admission to hospital (T-0), at discharge from hospital (T-1), and 6 months post-STEMI (T-6). Plasma levels of miR-223-3p, miR-142-3p, miR-155-5p, miR-486-5p, miR-125a-5p, and miR-146a-5p, as well as of cfDNA and mtDNA, were measured by RT-qPCR. Results showed that the levels of all measured miRNAs, as well as of cfDNA and mtDNA, were the most increased at T-1, compared to the other two time points. In the plasma of STEMI patients with MACE compared to those without MACE, we determined increased levels of miRNAs, cfDNA, and mtDNA at T-1. Hence, we used the levels of all measured parameters at T-1 for further statistical analysis. Statistical analysis demonstrated that all six miRNAs and cfDNA plus mtDNA levels, respectively, were associated with MACE. The minimal statistical model that could predict MACE in STEMI patients was the combination of mtDNA and miR-142-3p levels, as evidenced by ROC analysis (AUC = 0.97, p < 0.001). In conclusion, the increased plasma levels of mtDNA, along with miR-142-3p, could be used to predict unfavorable outcomes in STEMI patients.
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页数:20
相关论文
共 35 条
[1]   Association of Mitochondrial DNA Copy Number With Cardiovascular Disease [J].
Ashar, Foram N. ;
Zhang, Yiyi ;
Longchamps, Ryan J. ;
Lane, John ;
Moes, Anna ;
Grove, Megan L. ;
Mychaleckyj, Josyf C. ;
Taylor, Kent D. ;
Coresh, Josef ;
Rotter, Jerome I. ;
Boerwinkle, Eric ;
Pankratz, Nathan ;
Guallar, Eliseo ;
Arking, Dan E. .
JAMA CARDIOLOGY, 2017, 2 (11) :1247-1255
[2]   MiR-223-3p levels in the plasma and atherosclerotic plaques are increased in aged patients with carotid artery stenosis; association with HDL-related proteins [J].
Barbalata, Teodora ;
Moraru, Oriana E. ;
Stancu, Camelia S. ;
Sima, Anca V. ;
Niculescu, Loredan S. .
MOLECULAR BIOLOGY REPORTS, 2022, 49 (07) :6779-6788
[3]   Increased miR-142 Levels in Plasma and Atherosclerotic Plaques from Peripheral Artery Disease Patients with Post-Surgery Cardiovascular Events [J].
Barbalata, Teodora ;
Moraru, Oriana E. ;
Stancu, Camelia S. ;
Devaux, Yvan ;
Simionescu, Maya ;
Sima, Anca V. ;
Niculescu, Loredan S. .
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2020, 21 (24) :1-20
[4]   Regulation of microRNAs in high-fat diet induced hyperlipidemic hamsters [J].
Barbalata, Teodora ;
Zhang, Lu ;
Dulceanu, Madalina D. ;
Stancu, Camelia S. ;
Devaux, Yvan ;
Sima, Anca V. ;
Niculescu, Loredan S. .
SCIENTIFIC REPORTS, 2020, 10 (01)
[5]   Extracellular mtDNA activates NF-κB via toll-like receptor 9 and induces cell death in cardiomyocytes [J].
Bliksoen, Marte ;
Mariero, Lars Henrik ;
Torp, May Kristin ;
Baysa, Anton ;
Ytrehus, Kirsti ;
Haugen, Fred ;
Seljeflot, Ingebjorg ;
Vaage, Jarle ;
Valen, Guro ;
Stenslokken, Kare-Olav .
BASIC RESEARCH IN CARDIOLOGY, 2016, 111 (04)
[6]   Increased circulating mitochondrial DNA after myocardial infarction [J].
Bliksoen, Marte ;
Mariero, Lars Henrik ;
Ohm, Ingrid Kristine ;
Haugen, Fred ;
Yndestad, Arne ;
Solheim, Svein ;
Seljeflot, Ingebjorg ;
Ranheim, Trine ;
Andersen, Geir Oystein ;
Aukrust, Pal ;
Valen, Guro ;
Vinge, Leif Erik .
INTERNATIONAL JOURNAL OF CARDIOLOGY, 2012, 158 (01) :132-134
[7]   Elevated Levels of Circulating DNA and Chromatin Are Independently Associated With Severe Coronary Atherosclerosis and a Prothrombotic State [J].
Borissoff, Julian I. ;
Joosen, Ivo A. ;
Versteylen, Mathijs O. ;
Brill, Alexander ;
Fuchs, Tobias A. ;
Savchenko, Alexander S. ;
Gallant, Maureen ;
Martinod, Kimberly ;
ten Cate, Hugo ;
Hofstra, Leonard ;
Crijns, Harry J. ;
Wagner, Denisa D. ;
Kietselaer, Bas L. J. H. .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2013, 33 (08) :2032-2040
[8]   Dysfunctional high-density lipoproteins have distinct composition, diminished anti-inflammatory potential and discriminate acute coronary syndrome from stable coronary artery disease patients [J].
Carnuta, Mihaela G. ;
Stancu, Camelia S. ;
Toma, Laura ;
Sanda, Gabriela M. ;
Niculescu, Loredan S. ;
Deleanu, Mariana ;
Popescu, Andreea C. ;
Popescu, Mihaela R. ;
Vlad, Adelina ;
Dimulescu, Doina R. ;
Simionescu, Maya ;
Sima, Anca V. .
SCIENTIFIC REPORTS, 2017, 7
[9]  
Collet JP, 2021, REV ESP CARDIOL, V74, DOI [10.1016/j.rec.2021.05.002, 10.1093/eurheartj/ehaa575]
[10]   Mitochondrial Biomarkers in Patients with ST-Elevation Myocardial Infarction and Their Potential Prognostic Implications: A Prospective Observational Study [J].
Cosentino, Nicola ;
Campodonico, Jeness ;
Moltrasio, Marco ;
Lucci, Claudia ;
Milazzo, Valentina ;
Rubino, Mara ;
De Metrio, Monica ;
Marana, Ivana ;
Grazi, Marco ;
Bonomi, Alice ;
Veglia, Fabrizio ;
Lauri, Gianfranco ;
Bartorelli, Antonio L. ;
Marenzi, Giancarlo .
JOURNAL OF CLINICAL MEDICINE, 2021, 10 (02) :1-10