MicroRNA-218-5p regulates inflammation response via targeting TLR4 in atherosclerosis

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 coeffici...

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Published in:	BMC cardiovascular disorders Vol. 23; no. 1; p. 122
Main Authors:	Chen, Jiajuan, Tang, Zusheng, Chen, Zhen, Wei, Yunjie, Liang, Hui, Zhang, Xiaoqiao, Gao, Zhen, Zhu, Hezhong
Format:	Journal Article
Language:	English
Published:	England BioMed Central Ltd 08-03-2023 BioMed Central BMC
Subjects:	Analysis Apoptosis Arteriosclerosis Atherosclerosis Atherosclerosis - metabolism Atherosclerosis - pathology Bioinformatics Blood pressure Cardiovascular disease Care and treatment Cell culture Cell viability Cholesterol Chromosome 5 Correlation analysis Data analysis Diabetes Diagnosis Gene expression Genetic aspects Health aspects Humans Inflammation Inflammation - genetics Inflammation - metabolism Inflammation response Lipoproteins Lipoproteins, LDL - metabolism Low density lipoprotein Macrophages Macrophages - metabolism MicroRNA MicroRNAs MicroRNAs - metabolism MiR-218-5p miRNA Patients Reporter gene Smooth muscle TLR4 TLR4 protein Toll-Like Receptor 4 - genetics Toll-Like Receptor 4 - metabolism Toll-like receptors Transfection Tumor necrosis factor-TNF China TLR4 MiR-218-5p Atherosclerosis Inflammation response
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1471-2261 1471-2261
DOI:	10.1186/s12872-023-03124-y