多个细胞应激通路与高同类素素性阿波利波蛋白E缺陷小鼠加速动脉样硬化的关联
Ji Zhou1, Geoff H Werstuck, Sárka Lhoták
1Henderson Research Centre and McMaster University, Hamilton, Ontario, Canada.
Circulation
|June 24, 2004
概括
在小鼠中,高 metionin 的饮食会诱导高homocysteinemia,并加速动脉样硬化. 这项研究将细胞内膜网膜应激,氧化应激和炎症与动脉样硬化病变的发展联系起来.
科学领域:
- 心血管生物学 心血管生物学
- 动脉样硬化研究 动脉样硬化研究
- 细胞压力机制 细胞压力机制
背景情况:
- 超同胞蛋白血症 (HHcy) 与阿波利波蛋白E缺乏 (apoE-/-) 的小鼠加速动脉样硬化有关.
- 细胞应激路径,如氧化应激,ER应激和炎症都与HHcy诱导的动脉动脉产生有关,但尚未完全理解.
研究的目的:
- 在动脉样硬化病变中研究HHcy和细胞压力标志物之间的关联.
- 阐明ER压力,氧化压力和炎症在apoE-/-小鼠动脉样硬化发展中的作用.
主要方法:
- ApoE-/-小鼠被食高甲素 (HM) 饮食以诱导HHcy,在早期 (4周) 和晚期 (18周) 病变阶段进行分析.
- 免疫组织化学染色评估了ER压力 (GRP78/94,-PERK,HSP47),氧化压力 (HSP70) 和炎症 (-IkappaB-alpha) 的标志物.
- 水乙染色评估了心动脉中的氧化应激.
主要成果:
- 在早期和晚期阶段,HM饮食显著增加了血类固醇和动脉样硬化病变大小.
- 在HM养小鼠的晚期病变中,ER压力 (GRP78/94,HSP47),氧化压力 (HSP70) 和炎症 (-IkappaB-alpha) 的标志物升高.
- 在早期病变中,巨细胞泡细胞中也增加了ER压力标志物,这表明早期参与.
结论:
- 细胞应激途径,特别是ER应激,与apoE-/-小鼠的动脉样损伤发展有显著的关联.
- 这些发现突显了HHcy和细胞应激之间的相互作用,推动了动脉样硬化进展.
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