Diagnosis potential of subarachnoid hemorrhage using miRNA signatures isolated from plasma-derived extracellular vesicles.

Diagnosis potential of subarachnoid hemorrhage using miRNA signatures isolated from plasma-derived extracellular vesicles.
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DOI:
10.3389/fphar.2023.1090389
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发表时间:
2023
影响因子:
5.6
通讯作者:
--
中科院分区:
医学2区
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--
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动脉瘤性蛛网膜下腔出血(aSAH)的诊断和临床管理目前受到缺乏反映疾病病理生理的可获得的分子生物标志物的限制。我们使用microRNAs (miRNAs)作为诊断方法来表征aSAH的血浆细胞外囊泡。目前尚不清楚它们是否能诊断和治疗aSAH。采用新一代测序(NGS)检测3例SAH患者和3例健康对照(hc)的血浆细胞外囊泡(外泌体)的miRNA谱。我们鉴定了4个差异表达的mirna,并使用定量实时聚合酶链反应(RT-qPCR)对113例aSAH患者、40例hcc、20只SAH模型小鼠和20只假小鼠进行了验证。外泌体miRNA NGS显示,6种循环外泌体miRNA在aSAH患者与hcc患者中存在差异表达,并且4种miRNA (miR-369-3p、miR-410-3p、miR-193b-3p和miR-486-3p)的水平存在显著差异。经过多变量logistic回归分析,只有miR-369-3p、miR-486-3p和miR-193b-3p能够预测神经预后。在SAH小鼠模型中,miR-193b-3p和miR-486-3p的高表达与对照组相比仍具有统计学意义,而miR-369-3p和miR-410-3p的表达水平较低。miRNA基因靶预测显示,6个基因与这4种差异表达的miRNA相关。循环外泌体miR-369-3p、miR-410-3p、miR-193b-3p和miR-486-3p可能影响细胞间通讯,并具有作为aSAH患者预后生物标志物的潜在临床应用价值。
The diagnosis and clinical management of aneurysmal subarachnoid hemorrhage (aSAH) is currently limited by the lack of accessible molecular biomarkers that reflect the pathophysiology of disease. We used microRNAs (miRNAs) as diagnostics to characterize plasma extracellular vesicles in aSAH. It is unclear whether they can diagnose and manage aSAH. Next-generation sequencing (NGS) was used to detect the miRNA profile of plasma extracellular vesicles (exosomes) in three patients with SAH and three healthy controls (HCs). We identified four differentially expressed miRNAs and validated the results using quantitative real-time polymerase chain reaction (RT-qPCR) with 113 aSAH patients, 40 HCs, 20 SAH model mice, and 20 sham mice. Exosomal miRNA NGS revealed that six circulating exosomal miRNAs were differentially expressed in patients with aSAH versus HCs and that the levels of four miRNAs (miR-369-3p, miR-410-3p, miR-193b-3p, and miR-486-3p) were differentially significant. After multivariate logistic regression analysis, only miR-369-3p, miR-486-3p, and miR-193b-3p enabled prediction of neurological outcomes. In a mouse model of SAH, greater expression of miR-193b-3p and miR-486-3p remained statistically significant relative to controls, whereas expression levels of miR-369-3p and miR-410-3p were lower. miRNA gene target prediction showed six genes associated with all four of these differentially expressed miRNAs. The circulating exosomes miR-369-3p, miR-410-3p, miR-193b-3p, and miR-486-3p may influence intercellular communication and have potential clinical utility as prognostic biomarkers for aSAH patients.
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