Front Immunol. 2026 Jul 9;17:1797028. doi: 10.3389/fimmu.2026.1797028. eCollection 2026.
ABSTRACT
BACKGROUND: Myocardial infarction (MI) remains a leading cause of cardiovascular mortality worldwide, underscoring the need for improved diagnostic and therapeutic strategies. Despite recent in clinical management, delayed diagnosis and complications such as adverse myocardial remodeling continue to compromise long-term outcomes. Identifying specific biomarkers and actionable therapeutic targets is therefore crucial for precision medicine in MI.
METHODS: We integrated MI-related datasets from the Gene Expression Omnibus (GEO) database and performed differential expression analysis alongside weighted gene co-expression network analysis (WGCNA) to identify key differentially expressed genes (DEGs). Machine learning algorithms were applied to screen diagnostic hub genes and evaluate their diagnostic performance. Two-sample Mendelian randomization (MR) analysis, primarily utilizing the random-effects inverse-variance weighting assessed causal relationships between candidate genes and MI risk. Immune profiling was conducted via immune cell infiltration deconvolution and scRNA-seq analysis. Finally, wet-lab validation was performed using quantitative real-time PCR (RT-qPCR), Western blot, and immunohistochemistry in an in vivo animal model.
RESULTS: Our analysis initially identified 15 key diagnostic genes. Through two-sample MR analysis, MYO6 exhibited a significant causal relationship with a reduced risk of MI. Immune infiltration analysis revealed significant enrichment of pro-inflammatory cells (neutrophils and monocytes) and a concomitant depletion of protective immune cells (resting natural killer cells and activated CD4 memory T cells) in MI patients. MYO6 expression correlated positively with protective immune cells and negatively with pro-inflammatory cells. Furthermore, scRNA-seq analysis showed that MYO6 was predominantly enriched in T cells and natural killer cells, potentially regulating their subset differentiation, inhibiting excessive intercellular communication, and promoting collagen-mediated tissue repair, thereby alleviating MI injury and enhancing plaque stability. In vivo experiments validated the successful establishment of the MI model, revealing that MYO6 was significantly downregulated at both the mRNA and protein levels in infarcted myocardium.
CONCLUSION: Through multidimensional analysis of clinical transcriptomic data and experimental validation in animal models, we have identified MYO6 as a potential novel diagnostic biomarker for MI, while highlighting the role of immune homeostasis in disease progression and MYO6 regulation. These findings provide crucial insights for the molecular diagnosis and targeted therapy of MI.
PMID:42495634 | PMC:PMC13391262 | DOI:10.3389/fimmu.2026.1797028