SGLT2 Inhibitor Might Prevent Atrial Fibrillation Related to Metabolic Syndrome via TNF-α Signaling Pathway: A Bioinformatic Study

Background

Sodium-glucose co-transporter 2 (SGLT2) inhibitors have shown promise in reducing atrial fibrillation (AF) risk, but their mechanism of action in metabolic syndrome (MetS)-related AF remains unclear. This study aims to elucidate the potential mechanisms by which SGLT2 inhibitors interfere with AF initiation in MetS through comprehensive bioinformatic analysis.

Methods

A network pharmacology bioinformatic approach was employed to predict the molecular targets of SGLT2 inhibitors. Public databases, including SwissTarget, GeneCards, OMIM, and STRING, were utilized to identify and analyze targets associated with MetS-related AF. Protein–protein interaction (PPI) networks were constructed, followed by gene ontology (GO) and KEGG pathway enrichment analyses to elucidate the biological processes and pathways involved.

Results

A total of 52 common targets were identified linking SGLT2 inhibitors with MetS-related AF. The analysis highlighted the TNF-α and AGE-RAGE signaling pathways as key mechanisms through which SGLT2 inhibitors may mitigate AF. Our investigation identified p38 and JNK, components of the TNF-α signaling pathway, as primary targets in reducing atrial remodeling and fibrosis.

Conclusions

This study provides insights into the potential mechanisms by which SGLT2 inhibitors influence AF pathogenesis in MetS. The findings suggest that targeting the TNF-α signaling pathway may be a promising therapeutic strategy, with further experimental validation needed to confirm these results.

Trial Registration: The authors have nothing to report.