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<p>ST-segment elevation myocardial infarction (STEMI), a critical manifestation of coronary artery disease, involves complex molecular mechanisms potentially linked to brown adipocyte (BA) biology. This study aimed to identify BA-related key genes and elucidate their roles in STEMI progression. Transcriptomic data from peripheral blood mononuclear cells (PBMCs) of STEMI patients and stable coronary artery disease (CAD) controls were obtained from the GEO database (GSE59867, GSE62646). A 102-gene brown adipocyte-related gene (BARG) set was curated from published literature. Differentially expressed genes (DEGs) were identified using limma, and weighted gene co-expression network analysis (WGCNA) combined with single-sample gene set enrichment analysis (ssGSEA) was applied to detect BARG-associated module genes. The intersection of DEGs and module genes yielded 20 candidate genes, which were further refined using LASSO regression and SVM-RFE machine learning algorithms, identifying ASGR2, MCEMP1, and PPARG as key genes consistently upregulated in STEMI across both datasets. A nomogram model incorporating these three genes achieved an area under the ROC curve (AUC) of 0.973, demonstrating excellent diagnostic performance. Gene set enrichment analysis (GSEA) revealed convergent enrichment of all three key genes in neutrophil degranulation and Toll-like receptor signaling cascades. Immune infiltration profiling using CIBERSORT identified significant increases in monocytes alongside decreases in resting NK cells and eosinophils in STEMI, with all three key genes showing significant correlations with these immune cell populations. Molecular docking identified shinpterocarpin as a candidate compound targeting PPARG with a suggestive binding affinity (-5.8&#xa0;kcal/mol), warranting further experimental validation. RT-qPCR in an independent preliminary clinical cohort (<i>n</i> = 5 per group) demonstrated upregulation of all three key genes in STEMI patients (<i>p</i> &lt; 0.05), consistent with bioinformatic predictions. This study identifies ASGR2, MCEMP1, and PPARG as BA-associated key genes in STEMI PBMC profiles and highlights their potential immune-metabolic relevance.</p> Graphical abstract <p></p>

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Identification and validation of brown adipocyte-related key genes in ST-segment elevated myocardial infarction

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月23日

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  • Hongmin Li,
  • Xiaolin Chen,
  • Changhui Ma,
  • Yuanyuan Wang

摘要

ST-segment elevation myocardial infarction (STEMI), a critical manifestation of coronary artery disease, involves complex molecular mechanisms potentially linked to brown adipocyte (BA) biology. This study aimed to identify BA-related key genes and elucidate their roles in STEMI progression. Transcriptomic data from peripheral blood mononuclear cells (PBMCs) of STEMI patients and stable coronary artery disease (CAD) controls were obtained from the GEO database (GSE59867, GSE62646). A 102-gene brown adipocyte-related gene (BARG) set was curated from published literature. Differentially expressed genes (DEGs) were identified using limma, and weighted gene co-expression network analysis (WGCNA) combined with single-sample gene set enrichment analysis (ssGSEA) was applied to detect BARG-associated module genes. The intersection of DEGs and module genes yielded 20 candidate genes, which were further refined using LASSO regression and SVM-RFE machine learning algorithms, identifying ASGR2, MCEMP1, and PPARG as key genes consistently upregulated in STEMI across both datasets. A nomogram model incorporating these three genes achieved an area under the ROC curve (AUC) of 0.973, demonstrating excellent diagnostic performance. Gene set enrichment analysis (GSEA) revealed convergent enrichment of all three key genes in neutrophil degranulation and Toll-like receptor signaling cascades. Immune infiltration profiling using CIBERSORT identified significant increases in monocytes alongside decreases in resting NK cells and eosinophils in STEMI, with all three key genes showing significant correlations with these immune cell populations. Molecular docking identified shinpterocarpin as a candidate compound targeting PPARG with a suggestive binding affinity (-5.8 kcal/mol), warranting further experimental validation. RT-qPCR in an independent preliminary clinical cohort (n = 5 per group) demonstrated upregulation of all three key genes in STEMI patients (p < 0.05), consistent with bioinformatic predictions. This study identifies ASGR2, MCEMP1, and PPARG as BA-associated key genes in STEMI PBMC profiles and highlights their potential immune-metabolic relevance.

Graphical abstract