Department of Cardiology, Taihe Hospital, Hubei University of Medicine, No. 32 Renminnan Road, Shiyan, 442000, Hubei, China.
Department of General Practitioner, Taihe Hospital, Hubei University of Medicine, No. 32 Renminnan Road, Shiyan, 442000, Hubei, China.
BMC Cardiovasc Disord. 2023 Mar 8;23(1):122. doi: 10.1186/s12872-023-03124-y.
To investigate the expression of miR-218-5p in atherosclerosis patients and its effect on ox-LDL induced THP-1-derived macrophage inflammatory response.
RT-qPCR detected the expression of serum miR-218-5p, and the diagnostic value of miR-218-5p was analyzed by ROC curve. Pearson correlation coefficient was used to evaluate the correlation between miR-218-5p and CIMT and CRP. THP-1 cells were treated with ox-LDL to construct foam cell model. The expression of miR-218-5p was regulated by in vitro transfection technique, and the effects of miR-218-5p on cell viability, apoptosis and inflammation were investigated. Luciferase reporter genes were used to analyze target genes of miR-218-5p in cell models.
The expression of miR-218-5p in the atherosclerosis cohort was significantly reduced, and miR-218-5p showed a good ability to distinguish patients from healthy people. Correlation analysis showed that the level of miR-218-5p was negatively correlated with the levels of CIMT and CRP. Cytological studies showed that the expression of miR-218-5p in macrophages decreased after ox-LDL induction. ox-LDL treatment on macrophages resulted in decreased cell viability, increased cell apoptosis and production of inflammatory cytokines, which contributed to the exacerbation of plaque formation. However, the above situation was reversed after upregulation of miR-218-5p. Bioinformatics analysis showed that TLR4 may be the target gene of miR-218-5p, and this hypothesis was proved by luciferase reporter gene assay.
The expression of miR-218-5p is reduced in atherosclerosis, and it may regulate the inflammatory response of atherosclerotic foam cells by targeting TLR4, suggesting that miR-218-5p may be a promising target for clinical atherosclerosis therapy.
研究 miR-218-5p 在动脉粥样硬化患者中的表达及其对 ox-LDL 诱导的 THP-1 源性巨噬细胞炎症反应的影响。
采用 RT-qPCR 检测血清 miR-218-5p 的表达，通过 ROC 曲线分析 miR-218-5p 的诊断价值。采用 Pearson 相关系数评估 miR-218-5p 与 CIMT 和 CRP 的相关性。用 ox-LDL 处理 THP-1 细胞构建泡沫细胞模型。采用体外转染技术调节 miR-218-5p 的表达，观察 miR-218-5p 对细胞活力、凋亡和炎症的影响。采用荧光素酶报告基因分析细胞模型中 miR-218-5p 的靶基因。
动脉粥样硬化组 miR-218-5p 的表达明显降低，miR-218-5p 具有良好的区分患者与健康人群的能力。相关性分析显示，miR-218-5p 水平与 CIMT 和 CRP 水平呈负相关。细胞学研究表明，ox-LDL 诱导后巨噬细胞中 miR-218-5p 的表达降低。ox-LDL 处理巨噬细胞导致细胞活力降低，细胞凋亡增加，炎症细胞因子产生增加，促进斑块形成加重。然而，上调 miR-218-5p 后，上述情况得到逆转。生物信息学分析表明，TLR4 可能是 miR-218-5p 的靶基因，荧光素酶报告基因实验证明了这一假设。
miR-218-5p 在动脉粥样硬化中表达降低，可能通过靶向 TLR4 调节动脉粥样硬化泡沫细胞的炎症反应，提示 miR-218-5p 可能是临床动脉粥样硬化治疗的有前途的靶点。
