Lipidomic analysis of variation in response to simvastatin in the Cholesterol and Pharmacogenetics Study.
Lipidomic analysis of variation in response to simvastatin in the Cholesterol and Pharmacogenetics Study.
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DOI：
10.1007/s11306-010-0207-x
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发表时间：
2010-06
期刊：
影响因子：
3.6
通讯作者：
Krauss, Ronald M.
中科院分区：
文献类型：
--
作者：
Kaddurah-Daouk, Rima;Baillie, Rebecca A.;Zhu, Hongjie;Zeng, Zhao-Bang;Wiest, Michelle M.;Nguyen, Uyen Thao;Watkins, Steven M.;Krauss, Ronald M.
他汀类药物通常用于降低心血管疾病风险，但治疗益处和低密度脂蛋白胆固醇（LDL-C）水平的降低因个体而异。其他影响，包括C反应蛋白（CRP）的降低，也有助于治疗反应。代谢组学提供了强有力的工具，映射的变化，他汀类药物治疗的途径。这可能会导致机制假说，提供深入了解药物反应的个体差异的基础。使用靶向脂质组学平台，我们在胆固醇和药物遗传学研究中从LDL-C反应分布的上尾和下尾定义了血液样本中的脂质变化。反应者的代谢变化比非反应者更全面。基线胆固醇酯和磷脂代谢产物与LDL-C对治疗的反应相关。CRP对治疗的反应与基线缩醛磷脂、炎症中涉及的脂质相关。与辛伐他汀的LDL-C或CRP反应相关的脂质变化没有重叠，这表明不同的代谢途径决定了他汀类药物对这两种生物标志物的影响。代谢特征可以提供关于他汀类药物反应和作用机制的变化的见解。本文的在线版本（doi：10.1007/s11306-010-0207-x）包含补充材料，可供授权用户使用。
Statins are commonly used for reducing cardiovascular disease risk but therapeutic benefit and reductions in levels of low-density lipoprotein cholesterol (LDL-C) vary among individuals. Other effects, including reductions in C-reactive protein (CRP), also contribute to treatment response. Metabolomics provides powerful tools to map pathways implicated in variation in response to statin treatment. This could lead to mechanistic hypotheses that provide insight into the underlying basis for individual variation in drug response. Using a targeted lipidomics platform, we defined lipid changes in blood samples from the upper and lower tails of the LDL-C response distribution in the Cholesterol and Pharmacogenetics study. Metabolic changes in responders are more comprehensive than those seen in non-responders. Baseline cholesterol ester and phospholipid metabolites correlated with LDL-C response to treatment. CRP response to therapy correlated with baseline plasmalogens, lipids involved in inflammation. There was no overlap of lipids whose changes correlated with LDL-C or CRP responses to simvastatin suggesting that distinct metabolic pathways govern statin effects on these two biomarkers. Metabolic signatures could provide insights about variability in response and mechanisms of action of statins. The online version of this article (doi:10.1007/s11306-010-0207-x) contains supplementary material, which is available to authorized users.
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