Xie Hongguang, Wang Yiqiang, Zhu Xing, Zhang Lili, Niu Heli, Jin Hongguang
School of Traditional Chinese Medicine, Baicheng Medical College, Baicheng, Jilin, China.
Department of Cardiology, The Affiliated Hospital of Changchun University of Chinese Medicine, Changchun, Jilin, China.
Front Cardiovasc Med. 2025 Aug 12;12:1622958. doi: 10.3389/fcvm.2025.1622958. eCollection 2025.
This study explores lactylation's pivotal role in the disease progression of heart failure (HF).
The GSE57345 dataset, encompassing 177 HF samples and 136 normal controls (CTL), was sourced from Gene Expression Omnibus (GEO). Differentially expressed genes between HF and CTL groups underwent enrichment analysis using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Weighted correlation network analysis (WGCNA) and unsupervised clustering were employed to identify HF-associated gene modules and subtypes, and these were intersected with lactate-related genes (LRGs), curated from the Molecular Signatures Database and GeneCards, to pinpoint hub genes implicated in lactylation-mediated HF (Lcy-HF). The least absolute shrinkage and selection operator (LASSO), XGBoost, Boruta algorithm, and protein-protein interaction (PPI) networks were utilized to identify these hub genes. The diagnostic potential and biological significance of these hub genes in HF progression were assessed using receiver operating characteristic (ROC) curves, gene set enrichment analysis (GSEA), and immune infiltration analysis.
In the comparison between HF and CTL samples, 91 upregulated and 88 downregulated genes were identified, primarily enriched in inflammatory responses and pathways. By intersecting 387 LRGs curated from databases, we pinpointed six hub genes implicated in Lcy-HF: GATA2, HBB, JAK2, STAT2, STAT4, and WARS2. Immune infiltration analysis further revealed that these Lcy-HF hub genes are associated with macrophage polarization.
Lactylation plays a crucial role in the pathogenesis of HF, with genes such as GATA2, HBB, JAK2, STAT2, STAT4, and WARS2 emerging as potential lactylation biomarkers for HF identification. The lactylation-macrophage polarization-inflammation axis stands out as a pivotal mechanism driving HF progression.
本研究探讨乳酰化在心力衰竭（HF）疾病进展中的关键作用。
来自基因表达综合数据库（GEO）的GSE57345数据集包含177个HF样本和136个正常对照（CTL）。HF组和CTL组之间差异表达的基因使用基因本体论（GO）和京都基因与基因组百科全书（KEGG）通路进行富集分析。采用加权相关网络分析（WGCNA）和无监督聚类来识别与HF相关的基因模块和亚型，并将这些与从分子特征数据库和基因卡片中整理出的乳酸相关基因（LRG）进行交叉分析，以确定参与乳酰化介导的HF（Lcy-HF）的枢纽基因。使用最小绝对收缩和选择算子（LASSO）、XGBoost、Boruta算法和蛋白质-蛋白质相互作用（PPI）网络来识别这些枢纽基因。使用受试者工作特征（ROC）曲线、基因集富集分析（GSEA）和免疫浸润分析评估这些枢纽基因在HF进展中的诊断潜力和生物学意义。
在HF样本与CTL样本的比较中，鉴定出91个上调基因和88个下调基因，主要富集于炎症反应和通路。通过交叉分析从数据库中整理出的387个LRG，我们确定了6个与Lcy-HF相关的枢纽基因：GATA2、HBB、JAK2、STAT2、STAT4和WARS2。免疫浸润分析进一步表明，这些Lcy-HF枢纽基因与巨噬细胞极化相关。
乳酰化在HF发病机制中起关键作用，GATA2、HBB、JAK2、STAT2、STAT4和WARS2等基因成为用于HF识别的潜在乳酰化生物标志物。乳酰化-巨噬细胞极化-炎症轴是驱动HF进展的关键机制。
