骨髓细胞中循环氧基因酶-1缺乏会增加阿波利波蛋白E和低密度脂蛋白受体-null小鼠的早期动脉样硬化
Vladimir R Babaev1, Lei Ding, Jeff Reese
1Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA. vladimir.babaev@vanderbilt.edu
Circulation
|December 29, 2005
概括
骨髓细胞中循环氧基因酶-1 (COX-1) 缺乏会使小鼠的动脉样硬化恶化. 这表明血小板血栓素的产生不会促进早期病变的形成,而巨细胞中的COX-2上调是益风性.
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
- 动脉样硬化研究 动脉样硬化研究
背景情况:
- 循环氧基酶-1 (COX-1) 在动脉血症中发挥作用.
- 血小板中的COX-1产生血栓素 (TX),可能促进动脉样硬化和血栓形成.
研究的目的:
- 为了研究COX-1缺乏在骨髓衍生细胞中对小鼠早期动脉动脉生成的影响.
主要方法:
- 来自缺乏COX-1 (COX-1-/-) 的小鼠的骨髓被移植到接受LDL受体 (LDLR-/-) 和阿波利波蛋白E (apoE-/-) 的小鼠中.
- 评估了血小板TXA2,巨细胞TXA2代谢物,血清脂质和动脉样硬化病变的程度.
- 分析了巨细胞中的COX-2表达,并进行了胎儿肝细胞移植研究.
主要成果:
- 由于COX-1缺乏,导致血小板TXA2几乎完全丧失,并抑制了巨细胞/尿液TXA2代谢物.
- 血清脂质概况在不同组之间保持不变.
- 令人惊的是,动脉硬化病变显著增加在老鼠中,COX-1缺乏骨髓.
- 缺乏COX-1的巨细胞显示了脂多糖诱导的COX-2表达的增加.
- 胎儿肝细胞移植证实在COX-1-/- --> LDLR-/-小鼠中动脉样硬化增加了30%.
结论:
- 骨髓细胞中COX-1缺乏会在apoE-/-和LDLR-/-小鼠中加剧早期动脉样硬化.
- 血小板TX生产不会恶化早期动脉样硬化病变的形成.
- 在缺乏COX-1的巨细胞中,COX-2的升级是益风性.
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