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通过调节CD36表达,RFX1调节泡细胞的形成和动脉样硬化

Shuang Yang¹, Xiaoli Min², Longyuan Hu¹

¹Department of Dermatology, Second Xiangya Hospital, Central South University, Hunan Key Laboratory of Medical Epigenomics, Changsha 410011, China.

International immunopharmacology

|February 25, 2024

概括

调节因子X1 (RFX1) 缺乏通过增加泡细胞的形成促进动脉样硬化. 在巨细胞中减少RFX1表达是动脉样硬化发展的关键因素和潜在的治疗点.

科学领域:

免疫学免疫学免疫学
心血管研究研究心血管研究
分子生物学分子生物学

背景情况:

动脉样硬化 (AS) 是一种慢性炎症性疾病,其中巨细胞发挥着关键作用.
调节因子X1 (RFX1) 参与细胞分化,在AS患者的单细胞中观察到表达的减少.
在巨细胞衍生泡细胞的形成和AS的致病性方面,RFX1的特定功能仍然不清楚.

研究的目的:

研究RFX1在氧化低密度脂蛋白 (ox-LDL) 诱导的泡细胞形成中的作用.
确定RFX1对CD36表达及其转录调节的影响.
在体内阐明RFX1缺乏对动脉样硬化发展的影响.

主要方法:

在暴露于ox-LDL的小鼠腹膜巨细胞 (PMA) 中操纵RFX1表达 (上调/沉默).
使用ApoE-/-Rfx1f/f和ApoE-/-Rfx1f/f的Lyz2-Cre小鼠模型被养高脂肪饮食.
采用双 luciferase 记者测试来分析 RFX1 对 CD36 转录的调节.

主要成果:

在牛-LDL诱导的泡细胞中,RFX1的表达减少,与巨细胞的脂质吸收相反相关.
骨髓细胞中的RFX1缺乏会在ApoE-/-小鼠中加剧动脉样硬化病变.
RFX1直接抑制CD36转录,从而减少了巨细胞中的脂质积累.

结论:

在巨细胞中减少RFX1表达是泡细胞形成和AS启动的关键因素.
RFX1作为CD36表达的抑制剂,调节巨细胞脂质代谢.
向RFX1为治疗动脉样硬化提供了一个潜在的新疗法策略.

关键词:

动脉样硬化是一种动脉样硬化.泡细胞是一种泡细胞.巨细胞是一个巨细胞.一个 RFX1 的 RFX1 .ox-LDL 的使用情况.

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