脂质代谢异常和动脉样硬化:对器官功能调节和铁亡的新视角
Xize Wu1, Yuxi Huang1, Jiaqi Ren1
1The First Clinical College, Liaoning University of Traditional Chinese Medicine, Shenyang, China.
Frontiers in immunology
|September 2, 2025
概括
动脉样硬化的进展涉及由脂质代谢驱动的铁,影响免疫微环境. 像CYBB和HMOX1这样的关键基因调节这个过程, 提供潜在的治疗点.
科学领域:
- 心血管生物学
- 细胞死亡机制
- 分子医学
背景情况:
- 动脉样硬化 (AS) 是心血管疾病的主要原因,与脂质积累有关.
- 铁死是一种依赖于铁的细胞死亡, 越来越多地被认为是AS病变的关键因素.
- 对于AS研究来说,了解脂质代谢中的铁绝症至关重要.
研究的目的:
- 在动脉样硬化中的脂质代谢背景下研究铁亡的机制.
- 在AS中确定调节铁和脂质代谢的关键基因.
- 探索这些基因对AS免疫微环境的影响.
主要方法:
- 不同基因表达分析和数据集挖掘 (GSE100927).
- 聚类,权重基因共表达网络分析 (WGCNA) 和机器学习 (LASSO,SVM-RFE,RF) 用于中心基因识别.
- 在体外验证使用ox-LDL诱导的细胞模型 (HUVECs,RAW 264.7) 和单细胞RNA测序分析.
主要成果:
- 鉴定出六种与动脉样硬化脂质代谢相关的铁代谢基因 (ASLMRFeGs),这些基因会影响免疫微环境.
- 机器学习发现了四个候选Hub基因 (TYROBP,CSF1R,LCP2,C1QA).
- 在体外研究证实,脂质代谢失调促进铁,其抑制改善细胞功能障碍. 在泡细胞,巨细胞,光滑肌细胞和T细胞中发现了5个验证的Hub基因 (CYBB,HMOX1,IL1B,TYROBP,CSF1R).
结论:
- 在AS中异常的脂质代谢通过特定的调节基因 (CYBB,HMOX1,IL1B,TYROBP,CSF1R) 驱动铁.
- 这些基因显著重塑AS的免疫微环境.
- 这些发现提供了有关AS病变的见解以及针对铁和脂质代谢的潜在治疗策略.
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