循环外泌体 circRNAs 可作为急性心肌梗死的诊断生物标志物。

Exosomal CircRNAs in Circulation Serve as Diagnostic Biomarkers for Acute Myocardial Infarction.

机构信息

Heart Center and Beijing Key Laboratory of Hypertension, Beijing Chao-Yang Hospital, Capital Medical University, 100020 Beijing, China.

Department of Cardiology, Beijing Chao-Yang Hospital, Capital Medical University, 100020 Beijing, China.

出版信息

Front Biosci (Landmark Ed). 2024 Apr 11;29(4):149. doi: 10.31083/j.fbl2904149.

DOI:10.31083/j.fbl2904149

PMID:38682191

Abstract

BACKGROUND

The diagnostic potential of circular RNAs (circRNAs) in circulating exosomes for acute myocardial infarction (AMI) is not well understood, despite existing research indicating their role in cardiovascular diseases. This study aimed to clarify the significance of exosomal circular RNAs as indicators for AMI.

METHODS

We examined 120 individuals diagnosed with AMI and 83 individuals with non-cardiogenic chest pain (NCCP), all previously enrolled in a conducted study. High-throughput sequencing to identify differentially expressed circRNAs in the circulating exosomes of AMI patients. To validate, we employed Real-Time polymerase chain reaction (RT-PCR) targeting five circRNAs that exhibited notable increase.

RESULTS

The sequencing identified 893 exosomal circRNAs with altered expression in AMI patients, including 118 up-regulated and 775 down-regulated circRNAs. Genes linked to these circRNAs were enriched in crucial Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, highlighting their direct relevance to AMI pathophysiology. Three exosomal circRNAs (hsa_circ_0001558, hsa_circ_0001535, and hsa_circ_0000972) showed significant up-regulation in AMI patients during the initial validation cohort. The corresponding area under the curve (AUC) values were 0.79, 0.685, and 0.683, respectively. Further validation of hsa_circ_0001558 in a second cohort showed a 4.45-fold increase in AMI patients, with AUC = 0.793. The rise was particularly noticeable in patients with non-ST-elevation myocardial infarction (NSTEMI) (2.80 times, AUC = 0.72) and patients with ST-elevation myocardial infarction (STEMI) (5.27 times, AUC = 0.831) compared to patients with NCCP.

CONCLUSIONS

Our findings demonstrate significant differences in the expression patterns of circRNAs in plasma exosomes between AMI patients and NCCP patients. Specifically, hsa_circ_0001558 appears as a promising indicator for AMI diagnosis. Further research is necessary to fully evaluate the diagnostic potential of exosomal circRNAs in the context of AMI, emphasizing the importance of these findings.

摘要

背景

尽管已有研究表明环状 RNA（circRNAs）在心血管疾病中的作用，但循环外泌体中 circRNAs 对急性心肌梗死（AMI）的诊断潜力仍不明确。本研究旨在阐明外泌体环状 RNA 作为 AMI 标志物的意义。

方法

我们检测了 120 例 AMI 患者和 83 例非心源性胸痛（NCCP）患者，所有患者均先前参与了一项研究。采用高通量测序鉴定 AMI 患者循环外泌体中差异表达的 circRNAs。为了验证，我们采用实时聚合酶链反应（RT-PCR）针对 5 个circRNAs 进行检测，这些 circRNAs 表达显著增加。

结果

测序确定了 118 个上调和 775 个下调的 AMI 患者循环外泌体中改变表达的环状 RNA，包括 893 个外泌体环状 RNA。与这些 circRNAs 相关的基因在关键的京都基因与基因组百科全书（KEGG）途径中富集，突出了它们与 AMI 病理生理学的直接相关性。在最初的验证队列中，3 个外泌体 circRNAs（hsa_circ_0001558、hsa_circ_0001535 和 hsa_circ_0000972）在 AMI 患者中显著上调。相应的曲线下面积（AUC）值分别为 0.79、0.685 和 0.683。在第二个队列中进一步验证 hsa_circ_0001558 显示 AMI 患者的增幅为 4.45 倍，AUC = 0.793。与 NCCP 患者相比，非 ST 段抬高型心肌梗死（NSTEMI）患者（2.80 倍，AUC = 0.72）和 ST 段抬高型心肌梗死（STEMI）患者（5.27 倍，AUC = 0.831）的增幅更为显著。