Identification of lactylation-related hub genes as novel therapeutic and diagnostic targets for thoracic aortic dissection

IF 4.4 2区生物学 Q2 CELL BIOLOGY

Cellular signalling Pub Date : 2025-06-15 DOI:10.1016/j.cellsig.2025.111944

Jinxing Peng , Zhuohang Jiang , Jiayu Song , Jinze Chen , Ziyun Fu , Huizhe Zhang , Jianfan Zhen , Muhetaijiang Tuerdi , Mingyang Luo , Jinlin Wu , Tucheng Sun

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引用次数: 0

Abstract

Background

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.

Methods

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.

Results

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.

Conclusions

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.

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鉴定乳酸化相关中心基因作为胸主动脉夹层新的治疗和诊断靶点。

背景：胸主动脉夹层（TAD）是一种危及生命、死亡率高的心血管疾病。尽管乳酸化引起了越来越多的关注，但其在TAD中的作用仍然知之甚少。方法：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结果交叉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。来自GEO数据库的两个单细胞RNA测序（scRNA-seq）被用于评估细胞群和细胞间通信网络的乳酸化模式。采用受试者工作特征（ROC）分析评估生物标志物。结果：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，我们确定了包括LDHA在内的12种lrhg。在bapn诱导的小鼠模型中，LDHA抑制剂（Oxamate和FX11）显著降低死亡率，降低主动脉乳酸水平和蛋白乳酸化。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lrhg的最低AUC为0.8893。结论：本研究强调了乳酸酰化相关中心基因在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。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cellular signalling 生物-细胞生物学

CiteScore

8.40

自引率

0.00%

发文量

250

审稿时长

27 days

期刊介绍： Cellular Signalling publishes original research describing fundamental and clinical findings on the mechanisms, actions and structural components of cellular signalling systems in vitro and in vivo. Cellular Signalling aims at full length research papers defining signalling systems ranging from microorganisms to cells, tissues and higher organisms.