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循环外泌体长非编码 RNA 在急性心肌梗死患者中的研究

Circulating exosomal long non-coding RNAs in patients with acute myocardial infarction.

机构信息

Heart Center, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.

Beijing Key Laboratory of Hypertension Research, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.

出版信息

J Cell Mol Med. 2020 Aug;24(16):9388-9396. doi: 10.1111/jcmm.15589. Epub 2020 Jul 10.

Abstract

Exosomes are attracting considerable interest in the cardiovascular field as the wide range of their functions is recognized in acute myocardial infarction (AMI). However, the regulatory role of exosomal long non-coding RNAs (lncRNAs) in AMI remains largely unclear. Exosomes were isolated from the plasma of AMI patients and controls, and the sequencing profiles and twice qRT-PCR validations of exosomal lncRNAs were performed. A total of 518 differentially expressed lncRNAs were detected over two-fold change, and 6 kinds of lncRNAs were strikingly elevated in AMI patients with top fold change and were selected to perform subsequent validation. In the two validations, lncRNAs ENST00000556899.1 and ENST00000575985.1 were significantly up-regulated in AMI patients compared with controls. ROC curve analysis revealed that circulating exosomal lncRNAs ENST00000556899.1 and ENST00000575985.1 yielded the area under the curve values of 0.661 and 0.751 for AMI, respectively. Moreover, ENST00000575985.1 showed more significant relationship with clinical parameters, including inflammatory biomarkers, prognostic indicators and myocardial damage markers. Multivariate logistic model exhibited positive association of ENST00000575985.1 with the risk of heart failure in AMI patients. In summary, our data demonstrated that circulating exosomal lncRNAs ENST00000556899.1 and ENST00000575985.1 are elevated in patients with AMI, functioning as potential biomarkers for predicting the prognosis of pateints with AMI.

摘要

外泌体在心血管领域引起了相当大的关注,因为它们的广泛功能在急性心肌梗死 (AMI) 中得到了认可。然而,外泌体长非编码 RNA (lncRNA) 在 AMI 中的调节作用在很大程度上仍不清楚。从 AMI 患者和对照者的血浆中分离出外泌体,并对其外泌体 lncRNA 的测序图谱和两次 qRT-PCR 验证进行了分析。检测到 518 个差异表达的 lncRNA 超过两倍变化,并且在 AMI 患者中,有 6 种 lncRNA 的变化非常显著,并且 fold change 较高,选择进行后续验证。在两次验证中,lncRNA ENST00000556899.1 和 ENST00000575985.1 在 AMI 患者中明显高于对照组。ROC 曲线分析显示,循环外泌体 lncRNA ENST00000556899.1 和 ENST00000575985.1 对 AMI 的曲线下面积值分别为 0.661 和 0.751。此外,ENST00000575985.1 与包括炎症生物标志物、预后指标和心肌损伤标志物在内的临床参数具有更显著的关系。多变量逻辑模型显示,ENST00000575985.1 与 AMI 患者心力衰竭的风险呈正相关。总之,我们的数据表明,循环外泌体 lncRNA ENST00000556899.1 和 ENST00000575985.1 在 AMI 患者中升高,可作为预测 AMI 患者预后的潜在生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69f1/7417690/6492a2101592/JCMM-24-9388-g001.jpg

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