氧化胆酸通过对抗FXR和调节PD-1/mTORC1信号轴来减轻动脉样硬化

Feng Yang¹, Wenqiong Huang², Zongzhen Meng²

¹Department of Cardiology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China.

Redox biology

|March 3, 2026

概括

氧化胆酸 (HDCA) 疗法通过增强调控性T细胞 (Treg) 功能来减少动脉样硬化. HDCA对抗法尔内索伊德X受体 (FXR),改善Treg代谢和斑块内的免疫反应.

科学领域:

免疫代谢过程中的免疫代谢.
动脉样硬化的研究研究.
胆酸信号传递胆酸信号传递

背景情况:

胆汁酸调节代谢和炎症性疾病.
目前正在研究Farnesoid X受体 (FXR) 和氧胆酸 (HDCA) 在动脉样硬化 (AS) 中的作用.

研究的目的:

研究FXR和HDCA在AS开发中的作用.
阐明HDCA如何影响AS中的调节性T细胞 (Tregs) 的机制.

主要方法:

在AS患者中测量血清HDCA水平.
在体内给予全身性HDCA治疗.
采用 HDCA 治疗的 Tregs 转移到 ApoE 缺乏的小鼠中.
分析了Treg迁移,新陈代谢和信号通路 (FXR,PD-1/mTORC1,CPT1a).
确定ZNF671作为一个转录调节器.

主要成果:

在AS患者中,血清HDCA降低.
在体内,HDCA治疗减轻了斑块负担和减少了病变生长.
HDCA增强了Treg的迁移和积聚在斑块内.
HDCA通过对抗FXR来重新编程Treg代谢,增加糖解和ATP生产.
HDCA减轻了Treg迁移的ZNF671介导抑制.

结论:

HDCA对抗FXR,改善Treg免疫代谢和AS中的功能.
HDCA-FXR-PD-1/mTORC1轴代表了AS的一个新型免疫代谢标.
在动脉样硬化斑块内,HDCA增强了脂质处理和免疫调节.

关键词:

动脉样硬化是一种动脉样硬化.在 FXR 和 FXR 之间.葡萄糖溶解是什么? 葡萄糖溶解氧化胆酸是什么? 氧化胆酸是什么代谢过程中的代谢.在PD-1中使用PD-1.监管性T细胞是什么意思在Treg的迁移过程中.在 mTORC1 的情况下,mTORC1 是 mTORC1.

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