Evaluation of Toll-like Receptor 4 (TLR4) Involvement in Human Atrial Fibrillation: A Computational Study

Author:

Fagone Paolo1ORCID,Mangano Katia1ORCID,Basile Maria Sofia2ORCID,Munoz-Valle José Francisco3ORCID,Perciavalle Vincenzo2,Nicoletti Ferdinando1ORCID,Bendtzen Klaus4

Affiliation:

1. Department of Biomedical and Biotechnological Sciences, University of Catania, Via S. Sofia 89, 95123 Catania, Italy

2. Faculty of Medicine, Kore University, 94100 Enna, Italy

3. Institute for Research in Biomedical Sciences, University Center for Health Sciences, University of Guadalajara, Guadalajara 44100, Jalisco, Mexico

4. Institute for Inflammation Research, Rigshospitalet University Hospital, 2100 Copenhagen, Denmark

Abstract

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.

Publisher

MDPI AG

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