open access publication

Article, 2024

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

Genes, ISSN 2073-4425, Volume 15, 5, Page 634, 10.3390/genes15050634

Contributors

Fagone, Paolo 0000-0002-6694-1992 (Corresponding author) [1] Mangano, Katia 0000-0001-5920-4620 [1] Basile, Maria Sofia 0000-0002-4811-4694 [2] Muñoz-Valle, José Francisco 0000-0002-2272-9260 [3] Perciavalle, Vincenzo [2] Nicoletti, Ferdinando R 0000-0003-0917-443X [1] Bendtzen, Klaus [4]

Affiliations

  1. [1] University of Catania
    2. [NORA names: Italy; Europe, EU; OECD];
  2. [2] Faculty of Medicine, Kore University, 94100 Enna, Italy
    3. [NORA names: Italy; Europe, EU; OECD];
  3. [3] University of Guadalajara
    4. [NORA names: Mexico; America, Central; OECD];
  4. [4] Rigshospitalet
    5. [NORA names: Capital Region of Denmark; Hospital; Denmark; Europe, EU; Nordic; OECD]

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.

Keywords

MyD88, TICAM1, TLR2, TLR3, TLR4 signaling pathway, Toll-like receptor 4, Toll-like receptors, affected patients, analysis, associated with AF, association, atrial fibrillation, changes, computational study, computer, data, differentially expressed genes, downregulated differentially expressed genes, enrichment, enrichment analysis, evaluation, examination, expression patterns, fibrillation, gene expression patterns, genes, human atrial fibrillation, human transcriptome data, immune-related pathways, improve outcomes, involvement, involvement of Toll-like receptor 4, managing AF, meta-analysis, molecular aspects, nonspecific enrichment, outcomes, overlap, overrepresentation, pathophysiological role, pathway, pathway enrichment analysis, patients, patterns, receptor 4, receptors, role, signaling pathway, study, transcriptional changes, transcriptome data, treatment, upregulated genes

Data Provider: Digital Science

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