在Apoe-/-,Npc1-/-小鼠中发生自发性动脉栓塞和介质降解
Carrie L Welch1, Yu Sun, Brian J Arey
1Columbia University, Department of Medicine, P&S 8-401, 630 W 168th St, New York, NY 10032, USA. cbw13@columbia.edu
Circulation
|November 7, 2007
概括
尼曼-皮克C1 (Npc1) 基因缺陷通过促进前凝和蛋白酶活性增加动脉样硬化和血栓形成,导致斑块不稳定和介质退化.
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
- 疾病的遗传模型.
背景情况:
- 动脉硬性斑块破裂会导致急性冠状动脉综合征.
- 各种物种对斑块并发症的易感性各不相同.
- 斑块不稳定和血栓形成的机制尚不清楚.
研究的目的:
- 研究尼曼-皮克C1 (Npc1) 在动脉样硬化中的作用.
- 确定Npc1缺乏如何影响斑块形成和并发症.
- 确定影响斑块并发症的遗传因素.
主要方法:
- 产生了双重突变的小鼠 (Npc1-/- x Apoe-/-).
- 分析了动脉样硬化病变区域和形态.
- 评估了凝血参数和蛋白酶活性.
- 进行了遗传联系分析.
主要成果:
- 双重突变者表现出更大的病变,血栓和中间退化.
- 观察到缩短的凝血时间和升高的血-抗血复合物.
- 诱导了甲素K,增加了大动脉中的弹性酶活性.
结论:
- 细胞内胆固醇运输受损 (Npc1缺陷) 会促进动脉血症.
- 斑块并发症涉及促凝状态和蛋白酶活性升高.
- 遗传背景会影响对斑块不稳定性的易感性.
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