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Mitochondrial DNA Together with miR-142-3p in Plasma Can Predict Unfavorable Outcomes in Patients after Acute Myocardial Infarction
Authors:Teodora Barbalata  Alina I. Scarlatescu  Gabriela M. Sanda  Laura Toma  Camelia S. Stancu  Maria Dorobantu  Miruna M. Micheu  Anca V. Sima  Loredan S. Niculescu
Affiliation:1.Lipidomics Department, Institute of Cellular Biology and Pathology “Nicolae Simionescu” of the Romanian Academy, 8, B.P. Hasdeu Street, 050568 Bucharest, Romania;2.Department of Cardiology, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania;3.Department of Cardiology, Clinical Emergency Hospital of Bucharest, 014461 Bucharest, Romania
Abstract:
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 (T0), at discharge from hospital (T1), and 6 months post-STEMI (T6). 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 T1, 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 T1. Hence, we used the levels of all measured parameters at T1 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.
Keywords:biomarker   cardiovascular disease   cell-free DNA   microRNA   mitochondrial DNA   myocardial infarction
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