RationaleHypercholesterolemia is an important risk factor for cardiovascular diseases and death. This study performed pseudo‐targeted lipidomics to identify differentially expressed plasma lipids in hypercholesterolemia, to provide a scientific basis for the diagnosis and pathogenesis of hypercholesterolemia.MethodsPseudo‐targeted lipidomic analyses of plasma lipids from 20 patients with hypercholesterolemia and 20 normal control subjects were performed using liquid chromatography–mass spectrometry. Differentially expressed lipids were identified by principal component analysis and orthogonal partial least squares discriminant analysis. Receiver operating characteristic curves were used to identify differentially expressed lipids with high diagnostic value. The Kyoto Encyclopedia of Genes and Genomes pathway database was used to identify enriched metabolic pathways.ResultsWe identified 13 differentially expressed lipids in hypercholesterolemia using variable importance of projection > 1 and p < 0.05 as threshold parameters. The levels of eight sphingomyelins and cholesterol sulfate were higher and those of three triacylglycerols and lysophosphatidylcholine were reduced in hypercholesterolemia. Seven differentially expressed plasma lipids showed high diagnostic value for hypercholesterolemia. Functional enrichment analyses showed that pathways related to necroptosis, sphingolipid signaling, sphingolipid metabolism, and steroid hormone biosynthesis were enriched.ConclusionsThis pseudo‐targeted lipidomics study demonstrated that multiple sphingomyelins and cholesterol sulfate were differentially expressed in the plasma of patients with hypercholesterolemia. We also identified seven plasma lipids, including six sphingomyelins and cholesterol sulfate, with high diagnostic value.

中文翻译：

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基于伪靶向脂质组学鉴定多种血浆脂质作为高胆固醇血症的诊断生物标志物及其潜在机制

基本原理高胆固醇血症是心血管疾病和死亡的重要危险因素。本研究通过伪靶向脂质组学技术来鉴定高胆固醇血症中差异表达的血浆脂质，为高胆固醇血症的诊断和发病机制提供科学依据。 方法采用伪靶向脂质组学方法对20例高胆固醇血症患者和20例正常对照者的血浆脂质进行分析。液相色谱-质谱法。通过主成分分析和正交偏最小二乘判别分析鉴定差异表达的脂质。受试者工作特征曲线用于识别具有高诊断价值的差异表达脂质。使用京都基因和基因组百科全书通路数据库来识别富集的代谢通路。结果我们使用投影的可变重要性> 1和> 1确定了高胆固醇血症中的13种差异表达的脂质p< 0.05 作为阈值参数。高胆固醇血症时，八种鞘磷脂和硫酸胆固醇水平升高，三种三酰甘油和溶血磷脂酰胆碱水平降低。七种差异表达的血浆脂质对高胆固醇血症具有较高的诊断价值。功能富集分析表明，与坏死性凋亡、鞘脂信号传导、鞘脂代谢和类固醇激素生物合成相关的通路得到富集。结论这项伪靶向脂质组学研究表明，多种鞘磷脂和硫酸胆固醇在高胆固醇血症患者的血浆中存在差异表达。我们还鉴定了七种血浆脂质，包括六种鞘磷脂和硫酸胆固醇，具有很高的诊断价值。