在人类内皮细胞中,ox-LDL诱导了一种针对冠状动脉疾病风险丰富的非炎症反应
Jiahao Jiang1,2, Thomas K Hiron1,3, Anil Chalisey1,4
1Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Scientific reports
|July 2, 2025
概括
氧化低密度脂蛋白胆固醇 (ox-LDL) 改变了内皮细胞代谢,转录基因组和表观基因组,而不会引起炎症. 这项研究揭示了牛-LDL.
科学领域:
- 心血管生物学 心血管生物学
- 分子生物学分子生物学
- 基因组学就是基因组学.
背景情况:
- 氧化低密度脂蛋白胆固醇 (ox-LDL) 与动脉样硬化的发展有关.
- 在早期动脉生成中对ox-LDL的内皮细胞反应尚未完全理解.
研究的目的:
- 为了全面描述人类大动脉内皮细胞 (HAECs) 对ox-LDL的全基因组多组反应.
- 阐明在内皮细胞中由ox-LDL诱导的转录调节和表观遗传变化.
主要方法:
- 对暴露于ox-LDL.的初级HAEC进行全基因组多组组学分析 (代谢学,转录学,表观学).
- 对转录因子结合和基因表达的综合分析.
- 使用遗传风险数据识别基因与环境相互作用.
主要成果:
- 氧-LDL暴露诱导了HAEC代谢,转录和表观基因组的病原性变化,但不是典型的炎症表型.
- AP-1,NFE-2和CEBP转录因子与牛LDL诱导的转录有关.
- 氧-LDL通过转录因子结合部位的表观基因组重新连接促进了内皮细胞迁移.
- 在CALCRL/TFPI位点发现了rs62172376和牛-LDL之间的基因-环境相互作用,对冠状动脉疾病遗传风险进行了丰富.
结论:
- 氧-LDL在内皮细胞中引发了显著的转录和表观遗传变化,与炎症反应不同.
- 由ox-LDL驱动的表观基因组变化有助于内皮细胞迁移,并与冠状动脉疾病遗传风险有关.
- 提供了对内皮细胞对ox-LDL的反应及其与心血管疾病遗传倾向的相互作用的新见解.
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