氧化脂可以通过PERK/eIF2α轴提升ATF4,从而促进形大动脉病的发生
Xiaohua Zhu1, Linjie Yang1, Xu Han1
1Department of Cardiovascular Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450000, P.R. China.
Aging
|July 18, 2023
概括
氧化脂 (OxPL) 通过高调节激活转录因子4 (ATF4),促进M1巨细胞的极化和细胞的骨质分化,严重驱动性大动脉病 (CAVD).
科学领域:
- 心血管生物学 心血管生物学
- 分子医学是分子医学.
- 生物材料科学 生物材料科学
背景情况:
- 气性大动脉病 (CAVD) 是一种进展性疾病,其特征是大动脉结石化 (AVC).
- 在CAVD进展的基础上,精确的分子机制仍然不完全理解.
- 氧化脂 (OxPL) 和激活转录因子4 (ATF4) 都与心血管疾病有关.
研究的目的:
- 调查OxPL在CAVD进展中的关键作用.
- 为了阐明ATF4在OxPL介导的AVC中的参与.
- 探索将OxPL,ATF4,巨细胞极化和膜间歇细胞 (VIC) 骨质分化的分子途径.
主要方法:
- 生物信息学分析以确定CAVD.中差异表达的基因.
- 通过高胆固醇 (HC) 饮食诱导的大动脉结石化 (AVC) 的小鼠模型.
- 对小鼠膜间歇细胞 (VICs) 的隔离和骨质诱导.
- 同时培养VICs与OxPL刺激的巨细胞.
- 在VIC和in vivo中对ATF4的功能增加和丧失实验.
- 对巨分极和VIC骨质原体分化标记物的分析 (BMP2,OPN,骨质卡尔辛).
- 对PERK/eIF2α信号通路的研究.
主要成果:
- 在大动脉膜组织和骨质诱导VIC中,ATF4的表达很高.
- 降低ATF4显著缓解了VIC骨质性分化,并在体内停止了AVC.
- OxPL促进了M1巨细胞的两极分化,并调解了VIC的骨质分化.
- 通过PERK/eIF2α通路进行OxPL上调的ATF4表达.
结论:
- 在加速CAVD进展方面,OxPL起着至关重要的作用.
- 氧PL上调调节ATF4,导致M1巨细胞两极分化和VIC骨质分化.
- 针对OxPL-ATF4轴为CAVD提供了一个潜在的治疗策略.
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