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淋巴内皮细胞在动脉样硬化中的功能障碍和病理起源由单细胞转录学揭示

Qinhang Shen¹, Guangchao Gu¹, Dan Yang²

¹Department of Vascular Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.

|December 30, 2025

概括

淋巴内皮细胞 (LEC) 在动脉样硬化期间发生显著变化,显示出免疫作用和脂质处理的改变. 淋巴血管中的这些动态可能会推动心血管疾病的进展.

科学领域:

心血管生物学心血管生物学
免疫学免疫学免疫学
血管生物学血管生物学

背景情况:

动脉样硬化涉及复杂的血管和免疫细胞相互作用.
淋巴内皮细胞 (LEC) 在动脉样硬化中的特定作用尚未完全理解.
描述LEC动态对于理解动脉样硬化机制至关重要.

研究的目的:

研究动脉样硬化进展期间LECs的表型和功能变化.
在小鼠模型中识别LEC亚群及其转录重编程.
探索动脉样硬化中LECs的细胞起源和通信网络.

主要方法:

在基线,早期 (8周) 和晚期 (16周) 动脉样硬化阶段,从ApoE-/-小鼠获得大动脉细胞的单细胞RNA测序.
生物信息分析包括聚类,差异基因表达,轨迹推断和细胞间通信.
专注于描述LEC亚群及其动态变化的特征.

主要成果:

两个LEC亚种群显示出双相数值反应:早期疾病的扩张,晚期疾病的下降.
早期的LEC表现出免疫调节功能的改变,T细胞耐受性的降低和IL-7/IL-7R信号的增强.
LECs显示了下调的脂质处理基因 (Ldlr,Abca1) 和传统差异化和动脉样硬化特异性转基因与纤维细胞差异化的证据.

结论:

在动脉样硬化期间,LEC经历了显著的表型和功能变化.
不适应的分化和LECs损害的脂质运输/免疫调节可能会导致疾病的进展.
这项研究提供了血管疾病中淋巴参与的转录图谱,表明了治疗点.

关键词:

动脉样硬化动脉样硬化淋巴血管生成 (Lymphangiogenesis) 是一种导致淋巴血管发生的过程.淋巴内皮细胞是淋巴内皮细胞.

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