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氧化应激在肥厚型心肌病中的关键作用及机制:基于多组学分析和实验验证的系统探索

The Key Role and Mechanism of Oxidative Stress in Hypertrophic Cardiomyopathy: A Systematic Exploration Based on Multi-Omics Analysis and Experimental Validation.

作者信息

Zhang Sijie, Li Tianzhi, Sun Shiyi, Jiang Yujiao, Sun Yuxin, Meng Yan

机构信息

Key Laboratory of Pathobiology, Department of Pathophysiology, Ministry of Education, College of Basical Medical Sciences, Jilin University, 126 Xinmin Street, Changchun 130021, China.

出版信息

Antioxidants (Basel). 2025 May 7;14(5):557. doi: 10.3390/antiox14050557.

Abstract

Hypertrophic cardiomyopathy (HCM), characterised by abnormal ventricular thickening, involves complex mechanisms including gene mutations, calcium dysregulation, mitochondrial dysfunction, and oxidative stress. Oxidative stress plays a pivotal role in the progression of HCM by mediating cardiomyocyte injury and remodelling. This study systematically analysed HCM transcriptomic data using differential gene expression, weighted gene co-expression network analysis (WGCNA), and unsupervised consensus clustering to identify key genes and classify HCM subtypes. Four oxidative stress-related characteristic genes (, , , and ) were identified using LASSO regression, SVM-RFE, and Random Forest algorithms. Their functional significance was validated by immune infiltration analysis, drug prediction using the cMAP database, and molecular docking. Single-cell RNA sequencing revealed their cell-type-specific expression, and in vitro experiments confirmed their role in HCM. These findings provide insights into oxidative stress mechanisms and potential therapeutic targets for HCM.

摘要

肥厚型心肌病(HCM)的特征是心室异常增厚,涉及包括基因突变、钙调节异常、线粒体功能障碍和氧化应激在内的复杂机制。氧化应激通过介导心肌细胞损伤和重塑在HCM的进展中起关键作用。本研究使用差异基因表达、加权基因共表达网络分析(WGCNA)和无监督一致性聚类对HCM转录组数据进行系统分析,以鉴定关键基因并对HCM亚型进行分类。使用LASSO回归、支持向量机递归特征消除(SVM-RFE)和随机森林算法鉴定了四个与氧化应激相关的特征基因(、、和)。通过免疫浸润分析、使用cMAP数据库进行药物预测和分子对接验证了它们的功能意义。单细胞RNA测序揭示了它们的细胞类型特异性表达,体外实验证实了它们在HCM中的作用。这些发现为HCM的氧化应激机制和潜在治疗靶点提供了见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c66/12108539/ae2db7143932/antioxidants-14-00557-g001.jpg

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