综合的多组学分析揭示了动脉狭窄症中关键的枢纽基因和机制
Feng-Xia Wang1, Shuai Liu1, Hao-Qiang Guo2
1First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China.
Frontiers in cardiovascular medicine
|December 1, 2025
概括
在大动脉狭窄 (AS) 中识别致病基因至关重要. 这项研究发现了包括MMP9和PLAU在内的16个枢纽基因,有助于诊断AS并揭示它们在炎症中的作用.
科学领域:
- 心血管生物学 心血管生物学
- 分子病理学分子病理学
- 基因组学就是基因组学.
背景情况:
- 大动脉狭窄 (AS) 是结构性心脏病的重要危险因素,需要确定其潜在的遗传因素.
- 了解AS的致病基因可以为心脏病理和治疗策略提供新的见解.
研究的目的:
- 确定参与大动脉狭窄病变的关键基因.
- 探索已识别的基因的诊断潜力.
- 通过多组学方法阐明AS的分子机制.
主要方法:
- 使用 edgeR.R. 的差异基因表达分析 (批量-RNAseq).
- 基因本体学 (GO),KEGG途径和基因组丰富分析 (GSEA).
- 蛋白质基因测序,通过五种算法识别枢纽基因,以及ROC曲线分析.
- 单细胞RNA测序 (scRNAseq) 详细介绍AS的病变发生.
主要成果:
- 转录组分析显示MMP9,CXCL8和SPP1的高表达,AS中活性缺氧,炎症和纤维化.
- 蛋白质组学显示在化AS中增强了缺氧,TNF-α信号传递和细胞外矩阵形成.
- 包括ITGB3,ITGAV和MMP9在内的16个枢纽基因显示出高诊断效率 (AUC>0.75). 证实MMP9和PLAU在化门中表达高.
- scRNAseq显示MMP9和PLAU在内皮细胞,单细胞和巨细胞中,与单细胞/巨细胞分化,脂质代谢和炎症有关.
结论:
- 已识别的16个枢纽基因显示出有助于主动脉狭窄诊断的前途.
- MMP9和PLAU可以通过调节单细胞和巨细胞的炎症前驱活动,促进AS的发展.
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