托塞特拉皮不减少动脉样硬化超出阿托瓦斯塔丁,并诱导更多的预炎症病变比阿托瓦斯塔丁
Willeke de Haan1, Jitske de Vries-van der Weij, José W A van der Hoorn
1Leiden University Medical Center, Department of General Internal Medicine, Endocrinology, and Metabolic Diseases, 2300 RC Leiden, The Netherlands.
Circulation
|May 7, 2008
概括
胆固醇转移蛋白 (CETP) 抑制与torcetrapib降低了动脉样硬化,但没有改善阿托瓦斯塔丁. 托塞特拉皮也促进了不太稳定的斑块表型,增加了炎症.
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 研究动脉样硬化
背景情况:
- 胆固醇转移蛋白 (CETP) 的抑制旨在通过增加高密度胆固醇胆固醇来减少动脉样硬化.
- 在临床试验中,CETP抑制剂torcetrapib在与阿托瓦斯塔丁结合时没有益处,并增加了心血管风险.
- 这项研究研究了torcetrapib在人性化小鼠模型中的作用.
研究的目的:
- 为了评估torcetrapib的抗动脉增生潜力.
- 评估单独或与阿托瓦斯塔丁一起使用的torcetrapib的不良影响.
- 了解torcetrapib对动脉样硬化病变特征的影响.
主要方法:
- 人性化的APOE*3-Leiden.CETP (E3L.CETP) 鼠被食富含胆固醇的饮食14周.
- 小鼠没有接受任何药物,托塞特拉皮布,阿托瓦斯塔丁或两者的组合.
- 关键结局包括CETP活性,脂质水平,动脉样硬化病变大小和炎症标志物.
主要成果:
- 托塞特拉皮有效地降低了CETP活性,并增加了HDL胆固醇.
- 托塞特拉皮布和阿托瓦斯塔丁单独减少了病变大小;组合治疗没有提供额外的益处.
- 与阿托瓦斯塔丁相比,Torcetrapib增加了单细胞招募和病变炎症,降低了原蛋白含量.
结论:
- 单独使用torcetrapib可以减少动脉样硬化病变的大小,但不会增强阿托瓦斯塔丁的抗动脉质效应.
- 与阿托瓦斯塔丁相比,Torcetrapib治疗导致动脉样硬化病变,其表型不太稳定.
- 这些发现突出了超出脂质修饰的CETP抑制相关的潜在风险.
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