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MS4A1-PTGS2 轴诱导牛磺酸代谢重编程加重腹主动脉瘤进展。

MS4A1-PTGS2 axis induces taurine metabolic reprogramming to exacerbate abdominal aortic aneurysm progression.

机构信息

Department of Cardiovascular Surgery, Fujian Medical University Union Hospital, Fuzhou City, Fujian Province, 350001, China.

Department of Cardiovascular Surgery, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, 362002, China.

出版信息

Int J Med Sci. 2024 Aug 6;21(11):2052-2064. doi: 10.7150/ijms.99659. eCollection 2024.

DOI:10.7150/ijms.99659
PMID:39239552
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11373551/
Abstract

This study unveils the pivotal roles of taurine metabolic reprogramming and its implications in the development and progression of Abdominal Aortic Aneurysm (AAA). Leveraging an integrated approach that combines single-cell RNA sequencing (scRNA-seq) and Weighted Gene Co-expression Network Analysis (WGCNA), our research investigates the intricate transcriptional and gene expression dynamics crucial to AAA. Our findings uniquely link metabolic shifts to the integrity of the extracellular matrix (ECM) and the functionality of smooth muscle cells (SMCs), key elements in the pathology of AAA. Utilizing scRNA-seq data from a mouse model (GSE152583 dataset), we identified critical alterations in cellular composition during AAA progression, particularly highlighting shifts in fibroblasts and inflammatory cells. Concurrently, WGCNA of human AAA tissue samples has outlined distinct gene expression patterns correlated with disease severity and progression, offering comprehensive insights into both molecular and cellular disease mechanisms. Moreover, this study introduces innovative metabolic profiling techniques to identify differential metabolites in AAA, integrating extensive metabolomic analyses with pathway enrichment strategies. This novel approach has pinpointed potential biomarkers and therapeutic targets, notably within taurine metabolism pathways, crucial for crafting non-surgical interventions. By merging state-of-the-art bioinformatics with thorough molecular analysis, our study not only enhances the understanding of AAA's complex pathophysiology but also catalyzes the development of targeted therapeutic strategies. This research represents a significant advancement in the molecular characterization of AAA, with substantial implications for its future diagnosis and treatment strategies.

摘要

这项研究揭示了牛磺酸代谢重编程及其在腹主动脉瘤 (AAA) 发生和进展中的关键作用。本研究采用单细胞 RNA 测序 (scRNA-seq) 和加权基因共表达网络分析 (WGCNA) 相结合的综合方法,研究了 AAA 中复杂的转录和基因表达动态变化。我们的研究结果独特地将代谢变化与细胞外基质 (ECM) 的完整性和平滑肌细胞 (SMC) 的功能联系起来,这是 AAA 病理学的关键要素。利用来自小鼠模型的 scRNA-seq 数据 (GSE152583 数据集),我们在 AAA 进展过程中鉴定了细胞组成的关键变化,特别是强调了成纤维细胞和炎症细胞的变化。同时,对人 AAA 组织样本进行 WGCNA 分析,概述了与疾病严重程度和进展相关的独特基因表达模式,为分子和细胞疾病机制提供了全面的见解。此外,这项研究采用创新的代谢组学技术来鉴定 AAA 中的差异代谢物,将广泛的代谢组学分析与途径富集策略相结合。这种新方法确定了潜在的生物标志物和治疗靶点,特别是在牛磺酸代谢途径中,这对于制定非手术干预措施至关重要。通过将最先进的生物信息学与彻底的分子分析相结合,我们的研究不仅增强了对 AAA 复杂病理生理学的理解,还促进了靶向治疗策略的发展。这项研究代表了 AAA 分子特征的重大进展,对其未来的诊断和治疗策略具有重要意义。

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