Li Yawei, Wu Yubiao, Qin Xiude, Gu Jinchao, Liu Aijun, Cao Jiahui
Research Center of Basic Integrative Medicine, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China.
Encephalopathy Department, Shenzhen Traditional Chinese Medicine Hospital, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, China.
Front Cardiovasc Med. 2024 Jan 10;10:1322252. doi: 10.3389/fcvm.2023.1322252. eCollection 2023.
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.
动脉粥样硬化是一种以血管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,内皮细胞可发生内皮-间充质转化(EndMT),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)是一种传统中药配方,常用于治疗心血管疾病,但其分子机制仍不清楚。新出现的证据表明,竞争性内源性RNA(ceRNA)网络在动脉粥样硬化发病机制中起关键作用。在本研究中,我们通过整合来自基因表达综合数据库(GEO)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与EndMT相关的ceRNA网络。功能富集分析表明,这个与EndMT相关的ceRNA网络主要参与炎症反应。ROC曲线分析表明,鉴定出的枢纽基因能够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,IL1B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生物活性成分可以与关键的EndMT相关lncRNAs结合,包括AC003092.1、MIR181A1HG、MIR155HG、WEE2-AS1和MIR137HG,这表明DSY可能通过调节ceRNA网络减轻动脉粥样硬化中的EndMT。
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