Lysophospholipid profiles of apolipoprotein E-deficient mice reveal potential lipid biomarkers associated with atherosclerosis progression using validated UPLC-QTRAP-MS/MS-based lipidomics approach.
Lysophospholipid profiles of apolipoprotein E-deficient mice reveal potential lipid biomarkers associated with atherosclerosis progression using validated UPLC-QTRAP-MS/MS-based lipidomics approach.
复制标题
DOI：
10.1016/j.jpba.2019.03.062
复制
发表时间：
2019-07
影响因子：
3.4
通讯作者：
Yingfei Yan;Zhifeng Du;Chang Chen;Jiaxin Li;Xiang Xiong;Yang Zhang;Hongliang Jiang
中科院分区：
文献类型：
--
作者：
Yingfei Yan;Zhifeng Du;Chang Chen;Jiaxin Li;Xiang Xiong;Yang Zhang;Hongliang Jiang
溶血磷脂（Lyso-PLs）是脂质来源的信号分子，已被证明与动脉粥样硬化的进展有很强的相关性。在这项研究中，我们研究了高脂饮食对易患动脉粥样硬化的载脂蛋白E缺陷（ApoE−/−）小鼠和野生型C57 BL/6 J小鼠的Lyso-PL谱的影响，以找出与动脉粥样硬化相关的潜在生物标志物。首先，建立并验证了基于超高效液相色谱-四极杆线性离子阱质谱（UPLC-QTRAP-MS/MS）的溶血磷脂定量分析方法。其次，利用该方法定量在不同时间点收集的ApoE −/−小鼠和野生型C57 BL/6 J小鼠血浆样品中的169种靶向Lyso-PL。最后，通过静态代谢组学和时间依赖性分析，从37个Lyso-PL中筛选出12个与TC和LDL-C水平高度相关的Lyso-PC/15：0、18：1/Lyso-PI、22：5/Lyso-PI和22：4/Lyso-PI。同时，我们发现ApoE −/−小鼠和C57 BL/6 J小鼠的Lyso-PL谱是通过不同Lyso-PLs类代谢的改变来区分的，而C57 BL/6 J小鼠在高脂饮食和正常饮食下的Lyso-PLs谱是通过相同脂肪酸组成的Lyso-PLs含量的差异来区分的。总之，这些结果提供了与动脉粥样硬化相关的Lyso-PL谱的详细变化，并且具有合理变化趋势的差异Lyso-PL可以作为动脉粥样硬化进展的有希望的生物标志物。
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 ofApoE−/−mice and wild type C57BL/6 J mice collected at different time points. Finally, 12 of 37 differential Lyso-PLs 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 ofApoE−/−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.