Identification of DEGs Modulating Endothelial Inflammation in Response to IFN-γ and TMAO: A Bioinformatics Approach

Introduction: Endothelial inflammation is central to atherosclerosis and cardiovascular diseases, driven by interactions between inflammatory and metabolic factors. This bioinformatics approach examines the specific impacts of interferon-gamma (IFN-γ), a cytokine that promotes inflammation, and trimethylamine N-oxide (TMAO), a metabolite originating from the gut, on the transcriptomic profile of human aortic endothelial cells (HAECs). Methods: Gene expression profile data were obtained from the GEO database. Differential expression analysis was conducted utilizing GEO2R, and DEGs were selected based on specific cutoffs. Functional enrichment analyses were performed using DAVID. A protein-protein interaction (PPI) network was constructed with STRING and visualized in Cytoscape, with significant modules identified through MCODE. Results: Transcriptome data analysis identified 1008 DEGs in IFN-γ-treated cells (368 upregulated, 640 downregulated) and 23 DEGs in TMAO-treated cells (11 upregulated, 12 downregulated). IFN- γ upregulated processes related to signal transduction, cell adhesion, and angiogenesis, indicating a broad activation of immune and inflammatory pathways. TMAO induced minimal transcriptional changes. Discussion: Transcriptome analysis revealed that IFN-γ exerts a broad regulatory impact on endothelial cells, with significant upregulation of pathways linked to signal transduction, cell adhesion, and angiogenesis, consistent with its pro-inflammatory role. Hub gene analysis further confirmed repression of key mediators across JAK-STAT and related pathways, emphasizing IFN- γ’s dual role in activation and regulation. Conclusion: IFN-γ strongly modulated endothelial inflammation, both activating and suppressing immune responses, whereas TMAO elicited minimal transcriptional effects. The findings highlighted the distinct roles of inflammatory cytokines and metabolites in vascular inflammation, offering insights into mechanisms underlying cardiovascular disease progression.