骨髓细胞ACE塑造了PCSK-9诱导的动脉样硬化中的细胞代谢和功能
DuoYao Cao1, Suguru Saito1, LiMin Xu2
1Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, United States.
Frontiers in immunology
|November 6, 2023
概括
在髓状细胞中过度表达血管酶转化酶 (ACE) 会增强单细胞和巨细胞中的脂质代谢,防止动脉样硬化进展. 单细胞中的这种代谢转变是防止斑块积累的关键.
科学领域:
- 心血管生物学 心血管生物学
- 免疫代谢过程中的免疫代谢.
- 动脉样硬化病原体的产生
背景情况:
- 动脉样硬化病原包括受损的巨细胞脂质处理和慢性炎症.
- 巨细胞特异性血管酶转化酶 (ACE) 的过度表达可以保护小鼠免受动脉样硬化.
- ACE在外周血液单细胞,巨细胞前体中的作用尚不清楚.
研究的目的:
- 为了研究ACE在动脉样硬化中的外周血液单细胞中的作用.
- 为了确定单细胞中ACE过度表达是否会影响它们分化为巨细胞.
- 评估ACE介导的单细胞代谢变化对动脉样硬化进展的影响.
主要方法:
- 使用ACE10/10转基因小鼠,增加了巨细胞特异性ACE.
- 在动脉样硬化的条件下分析了外周血液单细胞群 (Ly-6Clo).
- 评估了分离单细胞中的脂质代谢,线粒体活性和ATP水平.
- 测量了小鼠的氧气消耗 (VO2),呼吸交换率 (RER) 和身体活动.
主要成果:
- 骨髓系细胞中的ACE过度表达改变了循环单细胞的新陈代谢.
- ACE10/10小鼠表现出增加的Ly-6Clo单细胞与增强的脂质代谢和线粒体活动.
- 在ACE10/10小鼠中观察到系统能量消耗增加 (VO2,RER,体力活动).
- 单细胞的功能性修改转移到分化的巨细胞,防止斑块的进展.
结论:
- 通过ACE介导的代谢表型存在于动脉样硬化的循环单细胞中.
- 骨髓细胞中的ACE过度表达增强了单细胞和巨细胞的脂质代谢.
- 单细胞和巨细胞的这种代谢重编程可以防止动脉样硬化病变的进展.
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