Department of Biomedical and Biotechnological Sciences, University of Catania, Via S. Sofia 89, 95123 Catania, Italy.
Faculty of Medicine, Kore University, 94100 Enna, Italy.
Genes (Basel). 2024 May 16;15(5):634. doi: 10.3390/genes15050634.
In the present study, we have explored the involvement of Toll-like Receptor 4 (TLR4) in atrial fibrillation (AF), by using a meta-analysis of publicly available human transcriptomic data. The meta-analysis revealed 565 upregulated and 267 downregulated differentially expressed genes associated with AF. Pathway enrichment analysis highlighted a significant overrepresentation in immune-related pathways for the upregulated genes. A significant overlap between AF differentially expressed genes and TLR4-modulated genes was also identified, suggesting the potential role of TLR4 in AF-related transcriptional changes. Additionally, the analysis of other Toll-like receptors (TLRs) revealed a significant association with TLR2 and TLR3 in AF-related gene expression patterns. The examination of MYD88 and TICAM1, genes associated with TLR4 signalling pathways, indicated a significant yet nonspecific enrichment of AF differentially expressed genes. In summary, this study offers novel insights into the molecular aspects of AF, suggesting a pathophysiological role of TLR4 and other TLRs. By targeting these specific receptors, new treatments might be designed to better manage AF, offering hope for improved outcomes in affected patients.
在本研究中，我们通过对公开的人类转录组数据进行荟萃分析，探讨了 Toll 样受体 4（TLR4）在心房颤动（AF）中的作用。荟萃分析显示，与 AF 相关的差异表达基因有 565 个上调和 267 个下调。通路富集分析突出了上调基因在免疫相关通路中的显著过度表达。AF 差异表达基因与 TLR4 调节基因之间也存在显著重叠，提示 TLR4 在 AF 相关转录变化中可能发挥作用。此外，对其他 Toll 样受体（TLRs）的分析显示，TLR2 和 TLR3 与 AF 相关基因表达模式显著相关。对与 TLR4 信号通路相关的 MYD88 和 TICAM1 基因的检查表明，AF 差异表达基因的富集程度显著但非特异性。总之，这项研究为 AF 的分子方面提供了新的见解，提示 TLR4 和其他 TLRs 在病理生理方面发挥作用。通过针对这些特定的受体，可能设计出新的治疗方法来更好地管理 AF，为受影响患者带来更好的治疗效果。
