BackgroundAtherosclerosis (AS) is one of the main causes of cardiovascular disease. AS plaques often occur in blood vessels with oscillatory blood flow and their formation can be regulated by microRNAs (miRNAs). The aim of this study is to identify the key miRNAs and molecular pathways involved in this pathological process.MethodsIn this study, gene chip data obtained from the GEO database was analyzed using the LIMMA package to find differentially expressed miRNAs (DE miRNAs) in the carotid arteries of ApoE−/− mice exposed to different blood flow rates. Predicted targets of the DE miRNAs were identified using the TargetScan, miRDB, and DIANA databases respectively, and the potential target genes (PTGs) were found by analyzing the common results of three databases. The DAVID database was used to enrich the PTGs based on gene ontology (GO) and pathway (Kyoto Encyclopedia of Genes and Genomes, KEGG), and the STRING database was used to uncover any protein-protein interactions (PPI) of the PTGs.ResultsThe networks of the DE miRNAs-PTGs, Pathway-PTGs-DE miRNAs, and PTGs PPI, were constructed using Cytoscape, and 11 up-regulated and 13 down-regulated DE miRNAs and 1479 PTGs were found. GO results showed that PTGs were significantly enriched in functions such as transcriptional regulation and DNA binding. KEGG results showed that PTGs were significantly enriched in inflammation-related mitogen-activated protein kinase (MAPK) and AS-related FOXO pathways. The PPI network revealed some key target genes in the PTGs.ConclusionsThe analysis of key miRNAs and molecular pathways that regulate the formation of AS plaques induced by oscillatory blood flow will provide new ideas for AS treatment.

中文翻译：

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暴露于扰动流动的 ApoE-/- 小鼠颈动脉中关键 microRNA 的鉴定

背景动脉粥样硬化（AS）是心血管疾病的主要原因之一。AS斑块通常发生在具有振荡血流的血管中，它们的形成可以受microRNAs (miRNAs)的调控。本研究的目的是确定参与这一病理过程的关键 miRNA 和分子通路。暴露于不同血流速率的 ApoE-/- 小鼠的动脉。DE miRNAs的预测靶点分别使用TargetScan、miRDB和DIANA数据库进行鉴定，并通过分析三个数据库的共同结果发现潜在靶基因（PTGs）。DAVID 数据库用于丰富基于基因本体 (GO) 和通路 (Kyoto Encyclopedia of Genes and Genomes, KEGG) 的 PTG，STRING 数据库用于揭示 PTG 的任何蛋白质-蛋白质相互作用 (PPI)。 结果使用 Cytoscape 构建了 DE miRNAs-PTGs、Pathway-PTGs-DE miRNAs 和 PTGs PPI 网络，发现了 11 个上调和 13 个下调的 DE miRNAs 和 1479 个 PTGs。GO结果表明，PTGs在转录调控和DNA结合等功能上显着富集。KEGG 结果显示，PTGs 在炎症相关的丝裂原活化蛋白激酶 (MAPK) 和 AS 相关的 FOXO 通路中显着富集。PPI 网络揭示了 PTG 中的一些关键靶基因。