School of Public Health, Baotou Medical College, Baotou, Inner Mongolia, China.
College of Life Sciences and Food Engineering, Inner Mongolia Minzu University, Tongliao, China.
Rapid Commun Mass Spectrom. 2024 May 15;38(9):e9723. doi: 10.1002/rcm.9723.
Hypercholesterolemia 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.
Pseudo-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.
We 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.
This 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.
高胆固醇血症是心血管疾病和死亡的一个重要危险因素。本研究进行了拟靶向脂质组学分析，以鉴定高胆固醇血症患者血浆中差异表达的脂质，为高胆固醇血症的诊断和发病机制提供科学依据。
采用液相色谱-质谱联用技术对 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拟靶向脂质组学分析。采用主成分分析和正交偏最小二乘判别分析鉴定差异表达脂质。采用受试者工作特征曲线鉴定具有高诊断价值的差异表达脂质。京都基因与基因组百科全书通路数据库用于鉴定富集的代谢通路。
采用变量重要性投影值>1 和 p<0.05作为阈值参数，我们在高胆固醇血症中鉴定出 13 种差异表达脂质。高胆固醇血症患者的八种鞘磷脂和胆固醇硫酸酯水平升高，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、鞘脂信号转导、鞘脂代谢和甾体激素生物合成相关的途径被富集。
本拟靶向脂质组学研究表明，高胆固醇血症患者血浆中存在多种鞘磷脂和胆固醇硫酸酯的差异表达。我们还鉴定出七种具有高诊断价值的血浆脂质，包括六种鞘磷脂和胆固醇硫酸酯。
