Impact of currently prescribed lipid-lowering drugs on plasma PCSK9 concentration: single or in combination study in rats

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• 作者：Yan Zhang (1)
  Jun Liu (1)
  Sha Li (1)
  Rui-Xia Xu (1)
  Jing Sun (1)
  Jian-Jun Li (1)
  
• 关键词：PCSK9 ; Statin ; Lipid profile ; Rat
• 刊名：Lipids in Health and Disease
• 出版年：2014
• 出版时间：December 2014
• 年：2014
• 卷：13
• 期：1
• 全文大小：247 KB
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• 作者单位：Yan Zhang (1)
  Jun Liu (1)
  Sha Li (1)
  Rui-Xia Xu (1)
  Jing Sun (1)
  Jian-Jun Li (1)
  
  1. Division of Dyslipidemia, State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, BeiLiShi Road 167, Beijing, 100037, China
  
• ISSN：1476-511X

文摘

Background An emerging data suggested a significant impact of statins on PCSK9 concentration, while the rapid impacts of other lipid-lowering drugs such as ezetimibe and xuezhikang alone or in combination on PCSK9 and lipid profile have not been assessed. This study aims to investigate whether an enhanced PCSK9 concentration by single or combined therapy of lipid-lowering drugs currently used precedes the changes of lipid profile in rats. Methods Sixty-three rats were randomly divided into six groups and orally administrated with placebo (N--3), ezetimibe 10?mg/kg daily, Xuezhikang 1200?mg/kg daily, ezetimibe 10?mg/kg plus Xuezhikang 1200?mg/kg daily, pitavastatin 10?mg/kg daily or pitavastatin 10?mg/kg plus ezetimibe 10?mg/kg daily for 3?days (N--0 for each group respectively). Blood samples were obtained at day 3 after orally administration. Plasma PCSK9 levels were determined by ELISA and lipid profile were measured by enzymatic assay. Results Ezetimibe, Xuezhikang and pitavastatin alone and Xuezhikang plus ezetimibe as well as pitavastatin plus ezetimibe increased PCSK9 levels by 124%, 56%, 111%, 63% and 204% respectively (p-lt;-.05 compared with placebo). However, Xuezhikang plus ezetimibe did not enhance greater PCSK9 levels compared to monotherapy. Ezetimibe and pitavastatin in combination induced higher PCSK9 levels than pitavastatin monotherapy or co-therapy with ezetimibe plus Xuezhikang. There was no significant difference between any groups with regard to lipid profile levels at day 3 (P-gt;-.05). Conclusions Elevated PCSK9 concentration by ezetimibe, Xuezhikang and pitavastatin alone or in combination was found prior to the alterations of lipid profile in rats. Combination of Xuezhikang and ezetimibe significantly attenuated increase in PCSK9 compared to ezetimibe plus pitavastatin, suggesting that the former combination may be better than the latter in future clinical application.