Decoding the Oral-Cardiac Axis: FCN1 and LYN as Key Players in the Molecular Dialogue between Acute Myocardial Infarction and Periodontitis

Abstract

BackgroundAcute myocardial infarction (AMI) and periodontitis (PD) have been epidemiologically linked, but the molecular mechanisms underlying this association remain elusive. We aimed to elucidate shared pathogenic signatures between AMI and PD using a comprehensive bioinformatics approach. MethodsWe integrated transcriptomic data from multiple Gene Expression Omnibus datasets, including an AMI cohort profiled from enriched circulating endothelial cells (GSE66360) with whole-blood validation (GSE48060), and PD gingival tissue cohorts (GSE16134 and GSE10334). Weighted gene co-expression network analysis, protein-protein interaction network analysis, and LASSO-based feature selection were applied. Functional enrichment, immune deconvolution, transcription factor-gene regulatory network analysis, and single-cell RNA sequencing analysis were performed to characterize shared molecular features. ResultsWe identified 95 shared differentially expressed genes (DEGs) between AMI and PD. By intersecting the shared upregulated DEGs with disease-associated WGCNA modules, we obtained 46 candidate shared genes. LASSO-based feature selection further highlighted FCN1 and LYN as overlapping candidates, which showed good discriminative performance in both training and external validation cohorts in ROC analyses. Enrichment analyses suggested that the shared signature was mainly related to myeloid cell migration, phagocytosis, and neutrophil-related inflammatory pathways (e.g., neutrophil extracellular trap formation). Immune deconvolution in PD gingival tissues suggested increased plasma cells and neutrophils and decreased resting memory CD4+ T cells; immune deconvolution results in the AMI cohort were interpreted cautiously due to the CEC-enriched sample source. Single-cell analysis revealed that FCN1 and LYN were predominantly expressed in macrophage/monocyte-derived populations. ConclusionsOur study suggests a shared inflammatory and immune-mediated transcriptomic program linking AMI and PD, and identifies FCN1 and LYN as candidate shared immune markers. These findings provide a molecular rationale for the oral-cardiovascular association and are hypothesis-generating, warranting future experimental and prospective validation.