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首页> 外文期刊>Journal of Pharmaceutical and Biomedical Analysis: An International Journal on All Drug-Related Topics in Pharmaceutical, Biomedical and Clinical Analysis >Lysophospholipid profiles of apolipoprotein E-deficient mice reveal potential lipid biomarkers associated with atherosclerosis progression using validated UPLC-QTRAP-MS/MS-based lipidomics approach
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Lysophospholipid profiles of apolipoprotein E-deficient mice reveal potential lipid biomarkers associated with atherosclerosis progression using validated UPLC-QTRAP-MS/MS-based lipidomics approach

机译：载脂蛋白E缺乏小鼠的溶血磷脂曲线揭示了使用验证的UPLC-QTRAP-MS / MS基础族学方法与动脉粥样硬化进展相关的潜在脂质生物标志物

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Lysophospholipids (Lyso-PLs) are lipid-derived signaling molecules which were demonstrated to have a strong correlation with the progression of atherosclerosis. In this study, we investigated the influence of high-fat diet on Lyso-PL profiles of atherosclerosis-prone apolipoprotein E-deficient (ApoE(-/-)) mice and wild type C57BL/6 J mice to find out the potential biomarkers associated with atherosclerosis. Firstly, the quantitative profiling method for Lyso-PLs based on ultra-performance liquid chromatography quadrupole linear ion trap mass spectrometry (UPLC-QTRAP-MS/MS) was established and validated. Secondly, this method was utilized to quantify 169 targeted Lyso-PLs in plasma samples of ApoE(-/-) mice and wild type C57BL/6 J mice collected at different time points. Finally, 12 of 37 differential LysoPLs were identified as more reliable biomarkers by integrating static metabolomics and time-dependent analyses, among which Lyso-PC/15:0, 18:1/Lyso-PI, 22:5/Lyso-PI and 22:4/Lyso-PI were highly correlated with TCand LDL-C levels. Meanwhile, we found that the Lyso-PL profiles of ApoE(-/-) mice and C57BL/6 J mice were distinguished by altered metabolism of different Lyso-PLs classes, while C57BL/6 J mice fed with high-fat diet and normal diet were discriminated by the content differences of Lyso-PLs with same fatty acid composition. In conclusion, these results provided detailed changes of Lyso-PL profiles associated with atherosclerosis and the differential Lyso-PLs with reasonable change trends may serve as promising biomarkers for atherosclerosis progression. (C) 2019 Elsevier B.V. All rights reserved.
机译：溶血磷脂（LySO-PL）是脂质衍生的信号传导分子，其证明与动脉粥样硬化的进展具有强烈的相关性。在这项研究中，我们研究了高脂饮食对动脉粥样硬化 - 俯卧载体E缺乏（ApoE（ - / - ））小鼠和野生型C57BL / 6 J小鼠的影响，以找出相关的潜在生物标志物随动脉粥样硬化。首先，建立并验证基于超高性能液相色谱四极性离子离子阱质谱（UPLC-QTRAP-MS / MS）的LySO-PL的定量分析方法。其次，利用该方法量化在不同时间点收集的ApoE（ - / - ）小鼠和野生型C57BL / 6 J小鼠的血浆样品中的169靶标样品中的169个靶向LySO-PL。最后，通过整合静态代谢组和时间依赖性分析，将37种差分液体的12种差异型液体标记物鉴定为更可靠的生物标志物，其中Lyso-PC / 15：0,18：1 / Lyso-Pi，22：5 / Lyso-Pi和22 ：4 / LySO-PI与TCAND LDL-C水平高度相关。同时，我们发现apoe（ - / - ）小鼠和c57bl / 6j小鼠的Lyso-pl型材通过不同的Lyso-PLS类的改变改变，而C57BL / 6 J小鼠饲喂高脂饮食和正常通过具有相同脂肪酸组成的LySO-PL的含量差异来歧视饮食。总之，这些结果提供了与动脉粥样硬化和具有合理变化趋势的差异Lyso-PL相关的Lyso-Pl曲线的详细变化可以作为动脉粥样硬化进展的有前途的生物标志物。 （c）2019 Elsevier B.v.保留所有权利。

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