乙-CoA:胆固醇乙转移酶抑制可以降低无脂蛋白E缺陷小鼠的动脉样硬化
J Kusunoki1, D K Hansoty, K Aragane
1Zena and Michael A. Wiener Cardiovascular Institute, Department of Medicine, Mount Sinai School of Medicine, New York, NY, USA.
Circulation
|May 31, 2001
概括
使用F-1394的Acyl-COA:胆固醇乙烯转移酶 (ACAT) 的部分抑制在没有毒性的小鼠中降低了动脉样硬化. 这表明ACAT抑制可能是治疗动脉样硬化的潜在治疗策略.
科学领域:
- 心血管研究研究心血管研究
- 药理学 药理学是指药理学的学科.
- 动脉样硬化研究 动脉样硬化研究
背景情况:
- 乙-COA:胆固醇乙转移酶 (ACAT) 将胆固醇转化为胆固醇.
- 巨细胞中的ACAT1有助于泡细胞的形成和动脉样硬化.
- 完全的ACAT1缺乏可能会导致毒性,影响组织胆固醇平衡.
研究的目的:
- 调查是否部分抑制ACAT1和ACAT2可以减少apoE缺乏小鼠的动脉样硬化.
- 评估部分ACAT抑制是否可以避免与完全缺乏相关的毒性.
主要方法:
- 在17周的时间里,ApoE缺乏的小鼠被食西方饮食.
- 小鼠没有接受ACAT抑制剂 (对照) 或F-1394 (300或900毫克/公斤).
- 分析了损伤区域,巨细胞染色和大动脉表面脂质染色.
主要成果:
- F-1394显著减少了亲密损伤面积的39-45%.
- 在F-1394治疗后,巨细胞染色减少了61-83%.
- 大动脉表面脂质染色减少了46-62%,没有明显的毒性.
结论:
- 用F-1394进行部分ACAT抑制,在apoE缺乏的小鼠中显示出抗动脉原效应.
- 治疗过程没有明显的系统性或血管壁毒性.
- 部分ACAT抑制显示出作为动脉样硬化治疗策略的潜力.
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