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超homocysteinemia促进炎症单细胞的产生和加速动脉样硬化在转基因cystathionineβ-合成酶缺乏的小鼠
Daqing Zhang1, Xiaohua Jiang, Pu Fang
1Department of Pharmacology and Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, PA 19140, USA.
Circulation
|October 28, 2009
概括
超同胞蛋白血症 (HHcy) 通过增加炎症单细胞子集驱动动动脉硬化. 这通过NAD(P) H氧化酶介导的氧化应激发生,促进单细胞在病变中的积累.
科学领域:
- 心血管生物学 心血管生物学
- 免疫学 免疫学 免疫学
- 代谢性疾病研究研究
背景情况:
- 超同胞蛋白血症 (HHcy) 是心血管疾病的一个已知的危险因素.
- 单细胞,关键的免疫细胞,有不同的子集参与动脉生成.
- 这项研究调查了HHcy如何影响单细胞异质性并导致动脉样硬化.
研究的目的:
- 为了确定HHcy是否调节单细胞异质性.
- 研究HHcy在促进动脉样硬化的作用.
- 阐明HHcy影响单细胞子集的机制.
主要方法:
- 开发了一种新的小鼠模型 (Tg-hCBS apoE(-/-) Cbs(-/-)) 患有严重的HHcy和高胆固醇血症.
- 使用了第二个HHcy小鼠模型 (Tg-S466L Cbs(-/-)) 缺乏超脂血症.
- 在血液,脏和骨髓中分析了单细胞群和子集.
- 用l-homocysteine和氧化应激抑制剂进行了体外实验.
主要成果:
- 严重的HHcy加速动脉样硬化和炎症性单细胞/巨细胞在病变中的积累.
- HHcy增加了整体单细胞种群,并扩大了炎症性Ly-6C (hi) 和Ly-6C (mid) 子集.
- 在体外,l-homocysteine通过NAD(P) H氧化酶介导的氧化应激诱导了Ly-6C (中) 单细胞分化.
结论:
- HHcy促进炎症单细胞子集的分化.
- HHcy通过增加炎症单细胞积累,有助于动脉样硬化病变的发展.
- NAD(P) H氧化酶依赖的氧化应激是将HHcy与动脉样硬化中的单细胞功能障碍联系起来的关键机制.
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