Ash2l在oxLDL诱导的内皮功能障碍和动脉样硬化中的功能性作用
Zhenghua Su1, Jinghuan Wang1, Chenxi Xiao1
1School of Pharmacy, Human Phenome Institute, Fudan University, Shanghai, 201203, China.
Cellular and molecular life sciences : CMLS
|January 27, 2024
概括
缺席的,小的,或同源的-Like 2 (Ash2l) 通过增加内皮细胞的脂质吸收来促进动脉样硬化. Ash2l Knockdown 减少了病变的形成,并提高了斑块的稳定性,这表明 Ash2l 是一种治疗点.
科学领域:
- 血管生物学 血管生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 动脉样硬化研究 动脉样硬化研究
背景情况:
- 内皮损伤和功能障碍是动脉样硬化发展的核心因素.
- Ash2l (Absent, small, or homeotic-Like 2) 是一种表观遗传调节剂,与血管损伤有关.
- Ash2l在动脉样硬化中的特定作用仍然在很大程度上是未知的.
研究的目的:
- 调查Ash2l在动脉样硬化病变发生过程中的作用.
- 阐明Ash2l在动脉样硬化中影响内皮细胞的分子机制.
- 评估Ash2l作为动脉样硬化的潜在治疗标.
主要方法:
- 在高胆固醇饮食养的ApoE-/-小鼠和经过氧化LDL (oxLDL) 处理的内皮细胞 (EC) 中评估了Ash2l表达.
- 研究了Ash2l通过H3K4三甲基化和NF-κB激活对食尸体受体转录的影响.
- 在ApoE-/-小鼠中进行ECs特定的Ash2l敲除,以评估对动脉样硬化病变形成和斑块稳定性的影响.
主要成果:
- 在动脉样硬化模型和oxLDL治疗的EC中,Ash2l表达升高.
- Ash2l通过H3K4三甲基化和增强的CD36-TLR4相互作用促进了扫除体受体转录和ECs的oxLDL吸收.
- 特定于ECs的Ash2l Knockdown显著减少了动脉样硬化病变的大小,并改善了小鼠的纤维帽稳定性.
结论:
- Ash2l作为一种新型表观遗传调节剂,促进内皮损伤和动脉样硬化.
- Ash2l通过调节清洁者受体和NF-κB信号传递,促进内皮细胞吸收oxLDL.
- 准Ash2l为动脉样硬化治疗提供了一个有前途的治疗策略.
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