Peng Jinxing, Jiang Zhuohang, Song Jiayu, Chen Jinze, Fu Ziyun, Zhang Huizhe, Zhen Jianfan, Tuerdi Muhetaijiang, Luo Mingyang, Wu Jinlin, Sun Tucheng
Department of Cardiac Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, China.
Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China.
Cell Signal. 2025 Jun 15;134:111944. doi: 10.1016/j.cellsig.2025.111944.
Thoracic aortic dissection (TAD) is a life-threatening cardiovascular disease with high mortality rates. Although lactylation has garnered increasing attention, its role in TAD remains poorly understood.
Lactylation-related genes (LRGs) were obtained from the MsigDB database. Lactylation-related hub genes (LRHGs) were identified by intersecting LRGs with differentially expressed genes and WGCNA results. Lactylation was assessed in a β-aminopropionitrile (BAPN)-induced mouse model and human aortic tissues. Two single-cell RNA sequencing (scRNA-seq) from the GEO database were utilized to evaluate lactylation patterns across cell populations and intercellular communication networks. Biomarkers were evaluated using receiver operating characteristic (ROC) analysis.
Elevated lactylation levels were observed in both TAD tissues and synthetic phenotype vascular smooth muscle cells. Through integrated analysis, we identified 12 LRHGs, which includes LDHA. In the BAPN-induced mouse model, LDHA inhibitors (Oxamate and FX11) significantly reduced mortality rates and decreased aortic lactate levels and protein lactylation. ScRNA-seq analytic results revealed that monocytes and macrophages exhibited the highest lactylation activity, which likely enhanced their inflammatory pathways and intercellular communication. ROC analysis showed the lowest AUC of 12 LRHGs is 0.8893.
This study highlights the critical role of lactylation-related hub genes in TAD, identifying potential therapeutic targets and diagnostic biomarkers, which provides novel insights into the molecular mechanisms underlying TAD.
胸主动脉夹层（TAD）是一种危及生命的心血管疾病，死亡率很高。尽管乳酸化已受到越来越多的关注，但其在TAD中的作用仍知之甚少。
从MsigDB数据库中获取乳酸化相关基因（LRGs）。通过将LRGs与差异表达基因和WGCNA结果相交来鉴定乳酸化相关枢纽基因（LRHGs）。在β-氨基丙腈（BAPN）诱导的小鼠模型和人主动脉组织中评估乳酸化。利用来自GEO数据库的两个单细胞RNA测序（scRNA-seq）来评估细胞群体间的乳酸化模式和细胞间通讯网络。使用受试者工作特征（ROC）分析评估生物标志物。
在TAD组织和合成表型血管平滑肌细胞中均观察到乳酸化水平升高。通过综合分析，我们鉴定出12个LRHGs，其中包括LDHA。在BAPN诱导的小鼠模型中，LDHA抑制剂（草氨酸盐和FX11）显著降低死亡率，并降低主动脉乳酸水平和蛋白质乳酸化。ScRNA-seq分析结果显示，单核细胞和巨噬细胞表现出最高的乳酸化活性，这可能增强了它们的炎症途径和细胞间通讯。ROC分析显示，12个LRHGs的最低AUC为0.8893。
本研究强调了乳酸化相关枢纽基因在TAD中的关键作用，确定了潜在的治疗靶点和诊断生物标志物，为TAD的分子机制提供了新的见解。
