Constructing a competitive endogenous RNA network of EndMT-related atherosclerosis through weighted gene co-expression network analysis.
Constructing a competitive endogenous RNA network of EndMT-related atherosclerosis through weighted gene co-expression network analysis.
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通过加权基因共表达网络分析构建与ENDMT相关的动脉粥样硬化的竞争性内源性RNA网络。
DOI：
10.3389/fcvm.2023.1322252
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发表时间：
2023
影响因子：
3.6
通讯作者：
Cao, Jiahui
中科院分区：
文献类型：
--
作者：
Li, Yawei;Wu, Yubiao;Qin, Xiude;Gu, Jinchao;Liu, Aijun;Cao, Jiahui
动脉粥样硬化是一种以内皮功能障碍和斑块形成为特征的慢性炎症性疾病。在促炎条件下，内皮细胞可以经历内皮-间质转化（EndMT），从而促进动脉粥样硬化的发展。然而，EndMT促进动脉粥样硬化的具体调控机制仍不清楚，需要进一步研究。丹参饮（DSY）是一种传统的中草药配方，常用于心血管疾病，但其分子机制仍不清楚。新的证据表明，竞争性内源性RNA（ceRNA）网络在动脉粥样硬化发病机制中起着关键作用。在这项研究中，我们通过整合基因表达Omnibus（GEO）数据库中的基因表达谱和加权基因共表达网络分析，构建了动脉粥样硬化进展过程中EndMT相关的ceRNA网络。功能富集分析显示，这种EndMT相关的ceRNA网络主要参与炎症反应。ROC曲线分析表明，所鉴定的枢纽基因可以有效区分正常血管和动脉粥样硬化病变。此外，Kaplan-Meier分析表明IL 1B的高表达显著预测动脉粥样硬化中的缺血事件。分子对接显示，大多数DSY生物活性组分可以结合关键的EndMT相关lncRNA，包括AC003092.1，MIR 181 A1 HG，MIR 155 HG，WEE 2-AS 1和MIR 137 HG，表明DSY可能通过调节ceRNA网络来减轻动脉粥样硬化中的EndMT。
Atherosclerosis is a chronic inflammatory disease characterized by endothelial dysfunction and plaque formation. Under pro-inflammatory conditions, endothelial cells can undergo endothelial-to-mesenchymal transition (EndMT), contributing to atherosclerosis development. However, the specific regulatory mechanisms by which EndMT contributes to atherosclerosis remain unclear and require further investigation. Dan-Shen-Yin (DSY), a traditional Chinese herbal formula, is commonly used for cardiovascular diseases, but its molecular mechanisms remain elusive. Emerging evidence indicates that competing endogenous RNA (ceRNA) networks play critical roles in atherosclerosis pathogenesis. In this study, we constructed an EndMT-associated ceRNA network during atherosclerosis progression by integrating gene expression profiles from the Gene Expression Omnibus (GEO) database and weighted gene co-expression network analysis. Functional enrichment analysis revealed this EndMT-related ceRNA network is predominantly involved in inflammatory responses. ROC curve analysis showed the identified hub genes can effectively distinguish between normal vasculature and atherosclerotic lesions. Furthermore, Kaplan-Meier analysis demonstrated that high expression of IL1B significantly predicts ischemic events in atherosclerosis. Molecular docking revealed most DSY bioactive components can bind key EndMT-related lncRNAs, including AC003092.1, MIR181A1HG, MIR155HG, WEE2-AS1, and MIR137HG, suggesting DSY may mitigate EndMT in atherosclerosis by modulating the ceRNA network.
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