BACKGROUND: Lipidomic biomarkers will facilitate the development of novel anti-atherosclerotic therapies. OBJECTIVE: To evaluate the responses of circulating biomarkers to simvastatin treatment. METHODS: A randomized, cross-over study in men with mixed dyslipidaemia was used to compare effects of simvastatin 40 mg/day with placebo. RESULTS:Plasma concentrations of nine fatty acids (FA; of 33 evaluated) were reduced significantly by simvastatin. No changes in the rates of FA synthesis or in hepatic lipase or lipoprotein lipase activities were apparent. Circulating proprotein convertase subtilisin/kexin type 9 (PCSK9) levels increased. CONCLUSION: We identified lipidomic biomarkers of simvastatin treatment effect that are consistent with statin inhibition of 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase (ClinicalTrials.gov: NCT00935259).
RCT Entities:
BACKGROUND: Lipidomic biomarkers will facilitate the development of novel anti-atherosclerotic therapies. OBJECTIVE: To evaluate the responses of circulating biomarkers to simvastatin treatment. METHODS: A randomized, cross-over study in men with mixed dyslipidaemia was used to compare effects of simvastatin 40 mg/day with placebo. RESULTS: Plasma concentrations of nine fatty acids (FA; of 33 evaluated) were reduced significantly by simvastatin. No changes in the rates of FA synthesis or in hepatic lipase or lipoprotein lipase activities were apparent. Circulating proprotein convertase subtilisin/kexin type 9 (PCSK9) levels increased. CONCLUSION: We identified lipidomic biomarkers of simvastatin treatment effect that are consistent with statin inhibition of 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase (ClinicalTrials.gov: NCT00935259).
Authors: Wu Yin; Ester Carballo-Jane; David G McLaren; Vivienne H Mendoza; Karen Gagen; Neil S Geoghagen; Lesley Ann McNamara; Judith N Gorski; George J Eiermann; Aleksandr Petrov; Michael Wolff; Xinchun Tong; Larissa C Wilsie; Taro E Akiyama; Jing Chen; Anil Thankappan; Jiyan Xue; Xiaoli Ping; Genevieve Andrews; L Alexandra Wickham; Cesaire L Gai; Tu Trinh; Alison A Kulick; Marcie J Donnelly; Gregory O Voronin; Ray Rosa; Anne-Marie Cumiskey; Kavitha Bekkari; Lyndon J Mitnaul; Oscar Puig; Fabian Chen; Richard Raubertas; Peggy H Wong; Barbara C Hansen; Ken S Koblan; Thomas P Roddy; Brian K Hubbard; Alison M Strack Journal: J Lipid Res Date: 2011-10-23 Impact factor: 5.922