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Digital PCR for Quantifying Circulating MicroRNAs in Acute Myocardial Infarction and Cardiovascular Disease
Published on: July 3, 2018
Mitochondrial DNA Together with miR-142-3p in Plasma Can Predict Unfavorable Outcomes in Patients after Acute
Teodora Barbalata1, Alina I Scarlatescu2,3, Gabriela M Sanda1
1Lipidomics Department, Institute of Cellular Biology and Pathology "Nicolae Simionescu" of the Romanian Academy, 8, B.P. Hasdeu Street, 050568 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.
Insights
Mitochondrial DNA and miR-142-3p in plasma can predict major adverse cardiovascular events in ST-segment elevation myocardial infarction patients. These biomarkers offer a new tool for assessing prognosis after heart attack.
Area of Science:
- Biochemistry
- Molecular Biology
- Cardiology
Background:
- Myocardial infarction (MI) remains a leading cause of mortality globally.
- Identifying reliable prognostic biomarkers for adverse outcomes post-MI is crucial for patient management.
- Current prognostic tools require enhancement for accuracy in predicting major adverse cardiovascular events (MACE).
Purpose of the Study:
- To evaluate plasma levels of six specific microRNAs (miRNAs), cell-free DNA (cfDNA), and mitochondrial DNA (mtDNA) as prognostic biomarkers for MACE in ST-segment elevation myocardial infarction (STEMI) patients.
- To determine the predictive value of these circulating biomarkers for unfavorable outcomes within six months post-STEMI.
Main Methods:
- Fifty STEMI patients were enrolled, with plasma samples collected at admission (T0), discharge (T1), and six months post-STEMI (T6).
- Quantitative reverse transcription polymerase chain reaction (RT-qPCR) was used to measure plasma levels of miR-223-3p, miR-142-3p, miR-155-5p, miR-486-5p, miR-125a-5p, miR-146a-5p, cfDNA, and mtDNA.
- Statistical analysis, including Receiver Operating Characteristic (ROC) curve analysis, was performed on T1 biomarker levels to assess MACE prediction.
Main Results:
- Plasma levels of all six miRNAs, cfDNA, and mtDNA were significantly elevated at T1 compared to T0 and T6.
- STEMI patients who experienced MACE showed higher T1 levels of miRNAs, cfDNA, and mtDNA than those without MACE.
- A combination model of mtDNA and miR-142-3p levels at T1 demonstrated high accuracy (AUC = 0.97) in predicting MACE.
Conclusions:
- Elevated plasma levels of mitochondrial DNA and miR-142-3p at hospital discharge are associated with an increased risk of MACE in STEMI patients.
- This combination of mtDNA and miR-142-3p serves as a potent, minimal biomarker model for predicting unfavorable outcomes after STEMI.
- These findings suggest potential for novel prognostic tools in acute myocardial infarction management.
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