MicroRNA profile of circulating CD4(+) T cells in aged patients with atherosclerosis obliterans.

MicroRNA profile of circulating CD4(+) T cells in aged patients with atherosclerosis obliterans.
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DOI:
10.1186/s12872-022-02616-7
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发表时间:
2022-04-15
影响因子:
2.1
通讯作者:
--
中科院分区:
医学4区
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--
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探讨老年动脉粥样硬化闭塞症(ASO)患者循环CD4+ T细胞中microRNAs (miRNAs)表达模式的特异性。利用从33名ASO患者和24名健康供者的外周血单个核细胞(PBMCs)中分离的CD4+ T细胞的miRNA微阵列进行了一项全面的miRNA表达研究。统计分析采用t检验,分层聚类采用平均联动法。结果经qRT-PCR验证。使用在线软件DIANA miRPath预测与验证mirna相关的假定靶向通路。基于两组之间1.3倍的表达变化截断值,我们鉴定了44个mirna,其中18个mirna显示错误发现率(FDR) p值< 0.05。存在分析验证12 microrna的差异,和6 microrna被证明是三个年龄组之间的差异表达(年龄:- 55年;56 - 75年;76 - 95年):的microrna miR-21 (p: 0.0008; 0.0009; 0.0022), miR-29b (p: 0.453; < 0.0001, < 0.0001),和mir - 374 b (p: < 0.0001, < 0.0001, 0.2493)显示,麻生太郎患者调节表达,而mir - 142 - 3 - p (p: < 0.0001, < 0.0001, < 0.0001), mir - 142 - 5 - p (p: < 0.0001, < 0.0001, < 0.0001),和mir - 150 (p: < 0.0001, < 0.0001;0.0001)在ASO患者中表达下调。经过验证的mirna参与了CD4+ T细胞的活化、增殖和迁移途径。老年ASO患者循环CD4+ T细胞可能表现出明显的分子特征。这是第一次从动脉粥样硬化中循环CD4+ T细胞中获得独特的、经过验证的miRNA谱。这种miRNA特征可能有助于阐明动脉粥样硬化的潜在机制。进一步的临床研究和深度报道将有助于确定这些动脉粥样硬化患者的预测和治疗靶点。在线版本包含补充材料,可在10.1186/s12872-022-02616-7获得。
To evaluate the specificity of the expression patterns of microRNAs (miRNAs) in circulating CD4+ T cells in aged patients with atherosclerosis obliterans (ASO). A comprehensive miRNA expression study was conducted using a miRNA microarray of CD4+ T cells isolated from peripheral blood mononuclear cells (PBMCs) of 33 patients with ASO and 24 healthy donors. A t test was used for statistical analysis, and the average linkage method was used for hierarchical clustering. The results were validated by qRT–PCR. Putative targeted pathways associated with validated miRNAs were predicted with the online software DIANA miRPath. We identified 44 miRNAs based on a cutoff value of a 1.3-fold change in expression between the two groups, with 18 miRNAs showing a false discovery rate (FDR) p value < 0.05. The qRT–PCR analysis validated differences in 12 miRNAs, and 6 miRNAs were proven to be differentially expressed among three age groups (age: 35–55 years; 56–75 years; 76–95 years): the miRNAs miR-21 (p: 0.0008; 0.0009; 0.0022), miR-29b (p: 0.453; < 0.0001; < 0.0001), and miR-374b (p: < 0.0001; < 0.0001; 0.2493) showed upregulated expression in patients with ASO, while miR-142-3p (p: < 0.0001; < 0.0001; < 0.0001), miR-142-5p (p: < 0.0001; < 0.0001; < 0.0001), and miR-150 (p: < 0.0001; < 0.0001; 0.0001) showed downregulated expression in patients with ASO. The validated miRNAs participated in CD4+ T cell activation, proliferation, and migration pathways. Circulating CD4+ T cells in aged patients with ASO may show a distinct molecular signature. This is the first time that a distinctive, validated miRNA profile from circulating CD4+ T cells in atherosclerosis has been presented. This miRNA signature may be used to help elucidate the underlying mechanism of atherosclerosis. Further clinical studies and in-depth reports will contribute to identifying predictive and therapeutic targets in these patients with atherosclerosis. The online version contains supplementary material available at 10.1186/s12872-022-02616-7.
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