巨中的Dicer通过促进线粒体氧化代谢来预防动脉样硬化
Yuanyuan Wei1,2, Judit Corbalán-Campos1, Rashmi Gurung1
1Experimental Vascular Medicine, Institute for Cardiovascular Prevention (Y.W., J.C.-C., R.G., L.N., M.Z., C.G., A.S.), Ludwig-Maximilians-University Munich, Germany.
Circulation
|May 12, 2018
概括
通过增强巨细胞的线粒体代谢和减少炎症和脂质积累,产生microRNA的Dicer酶可以预防动脉样硬化. 它的缺乏加速疾病,突出Dicer/miR-10a作为治疗点.
科学领域:
- 心血管生物学
- 分子医学
- 免疫学
背景情况:
- 替代性巨细胞激活对于解决炎症和预防动脉样硬化至关重要,这取决于线粒体的氧化代谢.
- 在动脉样硬化的过程中,巨细胞在控制胆固醇和甘油三中发挥着关键作用.
- 在巨细胞激活和动脉样硬化中,Dicer是一种微RNA生成酶的作用尚不清楚.
研究的目的:
- 研究Dicer在巨细胞激活中的作用及其对动脉样硬化的影响.
- 确定Dicer调节的特定的微RNA和mRNA目标,这些目标会影响动脉样硬化中的巨类型.
主要方法:
- 在高脂肪饮食中养的具有或没有巨细胞特异性Dicer删除的Apoe-/ -小鼠中研究了动脉样硬化.
- 使用RNA免疫沉,深度测序和microRNA功能查来识别Dicer调节的microRNA和标.
- 在体内使用位阻断剂评估了已识别的微RNA和位的治疗潜力.
主要成果:
- 在巨细胞中的Dicer删除加速了动脉样硬化,增加了炎症和脂质积累.
- 迪塞缺乏的巨细胞表现出线粒体脂肪酸氧化受损,泡细胞形成恶化.
- 恢复miR-10a,let-7b和miR-195a的氧化代谢;抑制miR-10a的核心压缩剂,促进脂肪酸氧化,并产生抗炎作用.
结论:
- 通过线粒体呼吸来调节巨细胞的炎症反应和脂质代谢,Dicer具有动脉保护作用.
- 在巨细胞中促进Dicer/miR-10a依赖的代谢重编程为预防动脉样硬化提供了潜在的治疗策略.
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