Atherosclerosis, a multifactorial and chronic immune inflammatory disorder, is the main cause of multiple cardiovascular diseases. Researchers recently reported that lncRNAs may exert important functions in the progression of atherosclerosis (AS). Some studies found that lncRNAs can act as ceRNAs to communicate with each other by the competition of common miRNA response elements. However, lncRNA-associated ceRNA network in terms of atherosclerosis is limited. In present study, we pioneered to construct and systematically analyze the lncRNA-mRNA network and reveal its potential roles in carotid atherosclerotic rabbit models. Atherosclerosis was induced in rabbits (n = 3) carotid arteries via a high-fat diet and balloon injury, while age-matched rabbits (n = 3) were treated with normal chow as controls. RNA-seq analysis was conducted on rabbits carotid arteries (n = 6) with or without plaque formation. Based on the ceRNA mechanism, a ternary interaction network including lncRNA, mRNA, and miRNA was generated and an AS-related lncRNA-mRNA network (ASLMN) was extracted. Furthermore, we analyzed the properties of ASLMN and discovered that six lncRNAs (MSTRG.10603.16, 5258.4, 12799.3, 5352.1, 12022.1, and 12250.4) were highly related to AS through topological analysis. GO and KEGG enrichment analysis indicated that lncRNA MSTRG.5258.4 may downregulate inducible co-stimulator to perform a downregulated role in AS through T cell receptor signaling pathway and downregulate THBS1 to conduct a upregulated function in AS through ECM-receptor interaction pathway. Finally, our results elucidated the important function of lncRNAs in the origination and progression of AS. We provided an ASLMN of atherosclerosis development in carotid arteries of rabbits and probable targets which may lay the foundation for future research of clinical applications.

中文翻译：

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系统分析lncRNA表达谱和动脉粥样硬化相关的lncRNA-mRNA网络，揭示在颈动脉粥样硬化兔模型中的功能性lncRNA。

动脉粥样硬化是一种多因素和慢性免疫炎症性疾病，是多种心血管疾病的主要原因。研究人员最近报道，lncRNA在动脉粥样硬化（AS）的进程中可能发挥重要作用。一些研究发现，lncRNA可以作为ceRNA，通过常见miRNA反应元件的竞争相互交流。然而，就动脉粥样硬化而言，与lncRNA相关的ceRNA网络是有限的。在本研究中，我们率先构建并系统分析了lncRNA-mRNA网络，并揭示了其在颈动脉粥样硬化兔模型中的潜在作用。 高脂饮食和球囊损伤在兔（n = 3）颈动脉中引起动脉粥样硬化，而与年龄匹配的兔（n = 3） ＝ 3）以正常食物作为对照。在 有或没有斑块形成的兔颈动脉（n = 6）上进行RNA-seq分析。基于ceRNA机制，生成了包括lncRNA，mRNA和miRNA的三元相互作用网络，并提取了与AS相关的lncRNA-mRNA网络（ASLMN）。此外，我们分析ASLMN的属性，发现有六个lncRNAs（MSTRG.10603.16，5258.4，12799.3，5352.1，12022.1和12250.4）的高度，通过拓扑分析与AS。GO和KEGG富集分析表明lncRNA MSTRG.5258.4可能通过T细胞受体信号通路下调诱导型共刺激物在AS中起下调作用，并通过ECM-受体相互作用通路下调THBS1在AS中起上调作用。最后，我们的结果阐明了lncRNA在AS起源和进展中的重要功能。我们提供了兔颈动脉动脉粥样硬化发展的ASLMN和可能的靶标，这可能为将来临床应用研究奠定基础。