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血浆中的线粒体 DNA 与 miR-142-3p 可预测急性心肌梗死患者的不良预后。

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

机构信息

Lipidomics Department, Institute of Cellular Biology and Pathology "Nicolae Simionescu" of the Romanian Academy, 8, B.P. Hasdeu Street, 050568 Bucharest, Romania.

Department of Cardiology, "Carol Davila" University of Medicine and Pharmacy, 050474 Bucharest, Romania.

出版信息

Int J Mol Sci. 2022 Sep 1;23(17):9947. doi: 10.3390/ijms23179947.

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.

摘要

心肌梗死是全球范围内导致死亡的主要原因之一,尽管人们做出了许多努力来寻找有效的预后生物标志物和治疗靶点。在本研究中,我们旨在评估六种已知与心血管疾病相关的 microRNA(miRNA)、循环细胞游离 DNA(cfDNA)和线粒体 DNA(mtDNA)在预测急性 ST 段抬高型心肌梗死(STEMI)后发生不良结局(如主要不良心血管事件[MACE])方面的潜在应用价值。

纳入 50 例 STEMI 患者,监测其 6 个月内发生 MACE 的情况。在入院时(T0)、出院时(T1)和 STEMI 后 6 个月(T6)采集血浆。通过 RT-qPCR 测定 miR-223-3p、miR-142-3p、miR-155-5p、miR-486-5p、miR-125a-5p 和 miR-146a-5p 以及 cfDNA 和 mtDNA 的血浆水平。结果显示,与另外两个时间点相比,所有测定的 miRNA 以及 cfDNA 和 mtDNA 的水平在 T1 时增加最多。在发生 MACE 的 STEMI 患者的血浆中,与未发生 MACE 的患者相比,我们在 T1 时确定了 miRNA、cfDNA 和 mtDNA 水平升高。因此,我们使用 T1 时所有测量参数的水平进行进一步的统计分析。

统计分析表明,所有 6 种 miRNA 和 cfDNA+mtDNA 水平分别与 MACE 相关。通过 ROC 分析(AUC = 0.97,p < 0.001),可以预测 STEMI 患者 MACE 的最小统计模型是 mtDNA 与 miR-142-3p 水平的组合。总之,mtDNA 与 miR-142-3p 血浆水平升高可用于预测 STEMI 患者的不良预后。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fcf/9456000/9d2e5d9083ce/ijms-23-09947-g001.jpg

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