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心脏miR-126-5p、miR-134-5p和miR-499a-5p在冠状动脉疾病所致心源性猝死中的诊断价值

Diagnostic value of cardiac miR-126-5p, miR-134-5p, and miR-499a-5p in coronary artery disease-induced sudden cardiac death.

作者信息

Li Linfeng, He Xiangwang, Liu Min, Yun Libing, Cong Bin

机构信息

Department of Forensic Pathology, West China School of Basic Medical Sciences and Forensic Science, Sichuan University, Chengdu, China.

Department of Forensic Medicine, Hebei Medical University, Shijiazhuang, China.

出版信息

Front Cardiovasc Med. 2022 Aug 25;9:944317. doi: 10.3389/fcvm.2022.944317. eCollection 2022.

Abstract

BACKGROUND

The identification of coronary artery disease-induced sudden cardiac death (CAD-SCD) has always been a medical challenge. MicroRNAs (miRNAs) played vital roles in pathogenesis processes and served as potential biomarkers for cardiovascular and many other diseases. The aim of this study was to investigate the diagnostic value of the specific miRNAs for CAD-SCD.

METHODS

A total of 30 autopsy-verified CAD-SCD victims were selected, including 18 individuals who experienced more than once asymptomatic myocardial ischemia (CAD-activated SCD) and 12 victims without prominent pathological features of insufficient blood supply (CAD-silent SCD). Meanwhile, 30 traumatic victims were enrolled as controls. Systematic postmortem examinations were performed in all study population. The expressions of cardiac miR-126-5p, miR-134-5p, and miR-499a-5p were analyzed by real-time quantitative polymerase chain reaction (RT-qPCR).

RESULTS

RT-qPCR showed significant downregulations of miR-126-5p and miR-499a-5p in CAD-SCD victims, with no obvious difference in miR-134-5p. Receiver-operating characteristic analysis revealed the diagnostic performance of miR-126-5p (areas under the curve [AUC] = 0.76) and validated miR-499a-5p (AUC = 0.82) as a sensitive marker. Additionally, the decreased expression of the two specific cardio-miRNAs was detected for discriminating CAD-silent SCD and CAD-activated SCD. Compared with the limited diagnostic value of single miR-126-5p and miR-499a-5p, their combination could achieve better discriminative capacity (AUC = 0.82, sensitivity = 91.7%, specificity = 77.8%).

CONCLUSION

Cardiac miR-126-5p and miR-499a-5p presented good diagnostic abilities for CAD-SCD, and their combination could help evaluate CAD condition. These targeted miRNAs as novel biomarkers are expected to be useful to discriminate the detailed causes in real SCD cases.

摘要

背景

冠心病诱发的心源性猝死(CAD-SCD)的识别一直是医学上的一项挑战。微小RNA(miRNA)在发病机制过程中发挥着重要作用,并作为心血管疾病和许多其他疾病的潜在生物标志物。本研究的目的是探讨特定miRNA对CAD-SCD的诊断价值。

方法

共选取30例经尸检证实的CAD-SCD受害者,其中18例经历过不止一次无症状心肌缺血(CAD激活型SCD),12例无明显供血不足病理特征(CAD隐匿型SCD)。同时,选取30例创伤受害者作为对照。对所有研究人群进行系统的尸检。通过实时定量聚合酶链反应(RT-qPCR)分析心脏miR-126-5p、miR-134-5p和miR-499a-5p的表达。

结果

RT-qPCR显示CAD-SCD受害者中miR-126-5p和miR-499a-5p显著下调,miR-134-5p无明显差异。受试者工作特征分析显示miR-126-5p的诊断性能(曲线下面积[AUC]=0.76),并验证miR-499a-5p(AUC=0.82)为敏感标志物。此外,检测到这两种特定心脏miRNA的表达降低,用于区分CAD隐匿型SCD和CAD激活型SCD。与单一miR-126-5p和miR-499a-5p有限的诊断价值相比,它们的组合可实现更好的鉴别能力(AUC=0.82,敏感性=91.7%,特异性=77.8%)。

结论

心脏miR-126-5p和miR-499a-5p对CAD-SCD具有良好的诊断能力,它们的组合有助于评估CAD病情。这些靶向miRNA作为新型生物标志物有望用于鉴别实际SCD病例的详细病因。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81d3/9457639/0a5b032a2bfd/fcvm-09-944317-g0001.jpg

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