加速动脉样硬化,大动脉动脉瘤形成和缺血性心脏病在阿波利波蛋白E/内皮氧化合成酶双敲击小鼠中的加速动脉样硬化,大动脉动脉瘤形成和缺血性心脏病
P J Kuhlencordt1, R Gyurko, F Han
1Cardiovascular Research Center, Cardiology Division, Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts, USA.
Circulation
|July 27, 2001
概括
内皮氧化合成酶 (eNOS) 缺乏会显著加快动脉样硬化,并导致西方饮食小鼠的冠心病. 这导致心力衰竭和大动脉并发症,不仅仅是由于高血压.
科学领域:
- 心血管研究研究心血管研究
- 动脉样硬化病原体的产生
- 鼠模型的模型
背景情况:
- 内皮氧化合成酶 (eNOS) 在血管健康中起作用.
- 动脉样硬化是一种复杂的心血管疾病.
- 了解影响动脉样硬化的遗传因素至关重要.
研究的目的:
- 研究eNOS缺乏对动脉样硬化发展的影响.
- 为了比较双淘汰赛 (apoE/eNOS-DKO) 和对照 (apoE-KO) 小鼠中的病变形成.
- 为了确定与eNOS缺乏相关的心血管并发症.
主要方法:
- 在apoE/eNOS-DKO小鼠和apoE-KO小鼠中病变发展的比较.
- 在16周的时间里,用西方式的饮食养动物.
- 评估动脉样硬化,冠状动脉样硬化,纤维化,心脏功能和大动脉完整性.
主要成果:
- 与apoE-KO对照组相比,apoE/eNOS-DKO小鼠的病变区域显著增加 (93.6%的雄性,59.2%的雌性).
- DKO动物出现了外周冠状动脉硬化,纤维化和心脏功能障碍 (增加LV壁厚度,减少分数缩短).
- 雄性DKO小鼠表现出自发的大动脉动脉瘤和剖析;在apoE-KO小鼠中没有观察到这些并发症.
结论:
- 在小鼠模型中,eNOS缺乏会加剧动脉样硬化,并诱导冠心病.
- 这项研究提出了第一个与心肌缺血症,心脏病发作和心力衰竭相关的远端冠状动脉硬化病的小鼠模型.
- 在DKO小鼠中,心血管并发症,包括缩和功能障碍,不仅仅归因于血压升高.
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