Background. Notwithstanding the mounting evidence to suggest that systemic lupus erythematosus (SLE) accelerates the progression of atherosclerosis, the mechanisms underlying this phenomenon are yet to be completely understood. This research examined the molecular mechanism behind this vascular complication. Methods. The Gene Expression Omnibus database was retrieved to acquire the gene expression datasets for SLE (GSE109248) and atherosclerosis (GSE100927). The shared differentially expressed genes (DEGs) of SLE and atherosclerosis were screened with the help of the “limma” package in R software, followed by function enrichment analysis, protein–protein interaction (PPI) network construction, key module analysis, hub gene selection, and coexpression analysis. Results. In GSE109248 and GSE100927, 1195 and 418 DEGs in totals were identified, respectively. Subsequently, we acquired 78 common DEGs (70 upregulated genes and eight downregulated genes) with the same expression trends by using the Venn diagram. Finally, 12 hub genes, including PTPRC, TYROBP, FCGR3A, ITGAX, LCP2, IL1B, IRF8, LILRB2, CD68, C1QB, CCR7, and C1QA were identified by using seven different algorithms in Cytohubba. The functional analysis illustrates that these genes were predominantly enriched in immune and inflammation response, lipid and atherosclerosis, and osteoporosis. These results indicate an important role of SLE in inducing excessive inflammation, which may be medicate by these hub genes and can induce osteoporosis and imbalance of the normal mineral balance in the body as well as lipid abnormalities, which eventually leads to premature onset of atherosclerosis. In total, nine transcription factors (TFs) that may participate in regulating the function of these genes were identified. All hub genes and four TFs were validated successfully. Conclusion. The results of our research show that SLE and atherosclerosis have common DEGs, pathophysiology, and hub genes. These findings can provide fresh evidence and insights into a further investigation into the mechanisms at play.

中文翻译：

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系统性红斑狼疮合并早发性动脉粥样硬化Hub基因及发病机制探讨

背景。尽管越来越多的证据表明系统性红斑狼疮（SLE）会加速动脉粥样硬化的进展，但这种现象背后的机制尚未完全了解。这项研究探讨了这种血管并发症背后的分子机制。方法。检索基因表达综合数据库以获得 SLE (GSE109248) 和动脉粥样硬化 (GSE100927) 的基因表达数据集。借助R软件中的“limma”软件包筛选SLE和动脉粥样硬化共有的差异表达基因（DEG），然后进行功能富集分析、蛋白质相互作用（PPI）网络构建、关键模块分析、枢纽基因选择和共表达分析。结果。在 GSE109248 和 GSE100927 中，分别鉴定出总共 1195 个和 418 个 DEG。随后，我们利用维恩图获得了表达趋势相同的78个常见DEG（70个上调基因和8个下调基因）。最后，在 Cytohubba 中使用七种不同的算法识别出 12 个 hub 基因，包括 PTPRC、TYROBP、FCGR3A、ITGAX、LCP2、IL1B、IRF8、LILRB2、CD68、C1QB、CCR7 和 C1QA。功能分析表明，这些基因主要富集于免疫和炎症反应、脂质和动脉粥样硬化以及骨质疏松症。这些结果表明，系统性红斑狼疮在诱发过度炎症方面发挥着重要作用，这可能是由这些枢纽基因引起的，可诱发骨质疏松、体内正常矿物质平衡失衡以及脂质异常，最终导致动脉粥样硬化过早发生。总共鉴定出九个可能参与调节这些基因功能的转录因子（TF）。所有中心基因和四个 TF 均已成功验证。结论。我们的研究结果表明，SLE 和动脉粥样硬化具有共同的 DEG、病理生理学和枢纽基因。这些发现可以为进一步研究起作用的机制提供新的证据和见解。