Inverse relationship between LDL cholesterol and PCSK9 plasma levels in dyslipidemic cynomolgus monkeys: Effects of LDL lowering by ezetimibe in the absence of statins

Hannes Hentze, Kristian K. Jensen, Ser Mien Chia, Douglas G. Johns, Rachel J. Shaw, Harry R. Davis, Shian Jiun Shih, Kenny K. Wong

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Objectives: To assess the lipid-lowering efficacy of ezetimibe in dyslipidemic cynomolgus monkeys comparing two dosing methods, and to evaluate PCSK9 plasma levels during dyslipidemia induction by feeding a high-fat/high-cholesterol diet (HFD), ezetimibe (Zetia®, Ezetrol®) treatment, ezetimibe washout, and HFD washout. Methods and results: Twenty dyslipidemic cynomolgus monkeys on HFD for seven months (LDL cholesterol 100-400mg/dL) were randomized into two groups and treated with ezetimibe for two weeks, either by oral gavage or by using food treats. The lipid-lowering effects of ezetimibe were identical between the two groups. After treatment, mean LDL cholesterol was decreased by 58% (174-72mg/dL), total cholesterol by 42% (241-138mg/dL), and PCSK9 levels were increased by 137% (147-314ng/mL). PCSK9 levels on regular diet before and after HFD were also inversely correlated to LDL cholesterol. Conclusions: In a cynomolgus dyslipidemia model, PCSK9 levels are inversely correlated with LDL cholesterol in the absence of statin treatment, regardless whether lipid changes are modulated by diet or ezetimibe treatment.

Original languageEnglish
Pages (from-to)84-90
Number of pages7
JournalAtherosclerosis
Volume231
Issue number1
DOIs
StatePublished - Nov 2013

Keywords

  • Dyslipidemia
  • Ezetimibe
  • Non-human primate
  • PCSK9

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