Identification of multiple plasma lipids as diagnostic biomarkers of hypercholesterolemia and the underlying mechanisms based on pseudo‐targeted lipidomics

Author:

Zhao Rui1ORCID,Tang Yuqing1,Cao Wenhui2,Zhao Lijuan2,Wu Zhifeng2,Chen Xianghui3,Li Yimin3,Jia Xiaoe34,Bai Haihua15

Affiliation:

1. School of Public Health Baotou Medical College Baotou Inner Mongolia China

2. College of Life Sciences and Food Engineering Inner Mongolia Minzu University Tongliao China

3. School of Basic Medicine and Forensic Medicine Baotou Medical College Baotou China

4. Inner Mongolia Key Laboratory of Hypoxic Translational Medicine, Baotou Medical College Inner Mongolia China

5. Affiliated Hospital of Inner Mongolia Minzu University Tongliao China

Abstract

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.

Funder

National Natural Science Foundation of China

Natural Science Foundation of Inner Mongolia Autonomous Region

Publisher

Wiley

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