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人类胸主动脉瘤中长链非编码 RNA 的差异表达谱。

Differential expression profile of long non-coding RNAs in human thoracic aortic aneurysm.

机构信息

Department of Cardiovascular Surgery, Institution of Cardiac Surgery, Changhai Hospital, The Second Military Medical University, Shanghai, China.

Department of Cardiology, Changhai Hospital, The Second Military Medical University, Shanghai, China.

出版信息

J Cell Biochem. 2018 Nov;119(10):7991-7997. doi: 10.1002/jcb.26670. Epub 2018 Jun 28.

DOI:10.1002/jcb.26670
PMID:29323743
Abstract

Thoracic aortic aneurysm (TAA) is progressive fatal aortic pathological dilation, which is characterized by increased proteoglycans and loss of elastic fibers. Recent advances in long non-coding RNAs (lncRNAs), an important regulator in many biological processes, suggested the close correlation between expression patterns and disease progression. In the present study, the ascending aortic tissues were collected from ascending TAA patients (n = 33) and organ donors (n = 16). Microarray analysis and real-time PCR were then applied to detect the lncRNA expression profiles. A total of 147 differentially expressed lncRNAs were determined, including 104 upregulated and 43 downregulated lncRNAs. Bioinformatics analysis showed 51.7% of differentially expressed lncRNAs were sense-overlapping, and most of the down-regulated lncRNAs were located on chromosome 1, 7, and 12. Subgroup analysis of TAA patients indicated that the expression of lnc-HLTF-5 was significantly higher in hypertension group than non-hypertension group (P < 0.05). Spearman correlation analysis further confirmed that the lnc-HLTF-5 level was positively correlated with the expanded ascending aortic diameter (r  = 0.483, P = 0.004) and MMP9 level (r  = 0.465, P = 0.006). Our results expanded the lncRNA expression patterns in aortic disease, and provided experimental basis for future investigation on TAA pathogenesis.

摘要

胸主动脉瘤(TAA)是一种进行性致命的主动脉病理性扩张,其特征是糖胺聚糖增多和弹性纤维丧失。长链非编码 RNA(lncRNA)的最新进展,作为许多生物过程中的重要调节因子,提示其表达模式与疾病进展密切相关。在本研究中,从升主动脉 TAA 患者(n=33)和器官供体(n=16)中收集升主动脉组织。然后应用微阵列分析和实时 PCR 检测 lncRNA 表达谱。确定了 147 个差异表达的 lncRNA,包括 104 个上调和 43 个下调的 lncRNA。生物信息学分析显示,差异表达的 lncRNA 中有 51.7%为顺式重叠,大多数下调的 lncRNA 位于染色体 1、7 和 12 上。TAA 患者的亚组分析表明,高血压组 lnc-HLTF-5 的表达明显高于非高血压组(P<0.05)。Spearman 相关分析进一步证实,lnc-HLTF-5 水平与扩张的升主动脉直径呈正相关(r=0.483,P=0.004)和 MMP9 水平呈正相关(r=0.465,P=0.006)。我们的研究结果扩展了主动脉疾病中的 lncRNA 表达模式,为 TAA 发病机制的进一步研究提供了实验基础。

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