外泌体 miR-152-5p 和 miR-3681-5p 可作为 ST 段抬高型心肌梗死的潜在生物标志物。

Exosomal miR-152-5p and miR-3681-5p function as potential biomarkers for ST-segment elevation myocardial infarction.

机构信息

Department of Ultrasound, People's Hospital of Longhua Shenzhen, Guangdong, China.

Department of Cardiology, People's Hospital of Longhua Shenzhen, Guangdong, China.

出版信息

Clinics (Sao Paulo). 2022 Jun 22;77:100038. doi: 10.1016/j.clinsp.2022.100038. eCollection 2022.

DOI:10.1016/j.clinsp.2022.100038

PMID:35751950

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9243048/

Abstract

BACKGROUND

The strain parameters of Real-Time Three-Dimensional Spot Tracking Echocardiography (RT3D-STE) are GLS, GAS, GRS, and GCS, while each index can significantly diagnose Acute Myocardial Infarction (AMI) patients, but none of them can distinguish between NSTEMI and STEMI. MicroRNAs (miRNAs) play essential roles in Acute Myocardial Infarction (AMI), but little is known about the value of exosome miRNA combined with Real-Time Three-Dimensional Spot Tracking Echocardiography (RT3D-STE) between ST-segment Elevation Myocardial Infarction (STEMI) and Non-ST-segment Elevation Myocardial Infarction (NSTEMI).

AIM

To estimate the exosomal miRNAs related to strain parameters of RT3D-STE as biomarkers for early detection of STEMI and NSTEMI.

METHODS

The present study collected plasma samples from thirty-four (34) patients with AMI (including STEMI and NSTEMI) and employed high-throughput sequence technology and real-time quantitative polymerase chain reaction (RT-qPCR) to identify the differentially expressed miRNAs. The Pearson correlation coefficient is used to measure the strength of a linear association between differentially expressed miRNAs and strain parameters of RT3D-STE.

RESULTS

Twenty-eight (28) differentially expressed exosomal miRNAs were universally identified between STEMI, NSTEM, and normal groups. Among them, there are 10 miRNAs (miR-152-5p, miR-3681-5p, miR-193a-5p, miR-193b-5p miR-345-5p, miR-125a-5p, miR-365a-3p, miR-4520-2-3p, hsa-miR-193b-3p and hsa-miR-5579-5p) with a Pearson correlation greater than 0.6 with RT3D-STE strain parameters. Especially, miR-152-5p and miR-3681-5p showed the most significant correlation with RT3D-STE strain parameters. Target genes of these 10 miRNAs are analyzed for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enrichment, and they were found to be mainly involved in the cellular metabolism processes and HIF-1 signaling pathway. RT-qPCR verified the significant differential expression of miR-152-5p and miR-3681-5p between STEMI and NSTEM groups.

CONCLUSION

RT3D-STE and exosome miRNAs can be used as a hierarchical diagnostic system in AMI. If the RT3D-STE is abnormal, the exosome miRNAs can be detected again to obtain more detailed and accurate diagnostic results between STEMI and NSTEM groups. Exosomal miR-152-5p and miR-3681-5p may serve as potential biomarkers for ST-segment elevation myocardial infarction.

摘要

背景

实时三维斑点追踪超声心动图（RT3D-STE）的应变参数为 GLS、GAS、GRS 和 GCS，每个指标均可显著诊断急性心肌梗死（AMI）患者，但均不能区分 NSTEMI 和 STEMI。微小 RNA（miRNA）在急性心肌梗死（AMI）中发挥重要作用，但对于外泌体 miRNA 联合 RT3D-STE 之间 ST 段抬高型心肌梗死（STEMI）和非 ST 段抬高型心肌梗死（NSTEMI）的价值知之甚少。

目的

评估与 RT3D-STE 应变参数相关的外泌体 miRNA 作为早期检测 STEMI 和 NSTEMI 的生物标志物。

方法

本研究收集了 34 例 AMI（包括 STEMI 和 NSTEMI）患者的血浆样本，采用高通量测序技术和实时定量聚合酶链反应（RT-qPCR）鉴定差异表达的 miRNA。Pearson 相关系数用于测量差异表达 miRNA 与 RT3D-STE 应变参数之间线性关联的强度。

结果

在 STEMI、NSTEM 和正常组之间普遍鉴定出 28 个差异表达的外泌体 miRNA。其中，有 10 个 miRNA（miR-152-5p、miR-3681-5p、miR-193a-5p、miR-193b-5p、miR-345-5p、miR-125a-5p、miR-365a-3p、miR-4520-2-3p、hsa-miR-193b-3p 和 hsa-miR-5579-5p）与 RT3D-STE 应变参数的 Pearson 相关系数大于 0.6。特别是 miR-152-5p 和 miR-3681-5p 与 RT3D-STE 应变参数相关性最显著。对这 10 个 miRNA 的靶基因进行基因本体论（GO）和京都基因与基因组百科全书（KEGG）通路富集分析，发现它们主要参与细胞代谢过程和 HIF-1 信号通路。RT-qPCR 验证了 miR-152-5p 和 miR-3681-5p 在 STEMI 和 NSTEMI 组之间的显著差异表达。

结论

RT3D-STE 和外泌体 miRNA 可作为 AMI 的分层诊断系统。如果 RT3D-STE 异常，可以再次检测外泌体 miRNA，以获得 STEMI 和 NSTEMI 组之间更详细和准确的诊断结果。外泌体 miR-152-5p 和 miR-3681-5p 可能作为 ST 段抬高型心肌梗死的潜在生物标志物。