Abstract
Lipid metabolites are indispensable regulators of physiological and pathological processes, including atherosclerosis and coronary artery disease (CAD). However, the complex changes in lipid metabolites and metabolism that occur in patients with these conditions are incompletely understood. We performed lipid profiling to identify alterations in lipid metabolism in patients with angina and myocardial infarction (MI). Global lipid profiling was applied to serum samples from patients with CAD (angina and MI) and age-, sex-, and body mass index-matched healthy subjects using ultra-performance liquid chromatography/quadruple time-of-flight mass spectrometry and multivariate statistical analysis. A multivariate analysis showed a clear separation between the patients with CAD and normal controls. Lysophosphatidylcholine (lysoPC) and lysophosphatidylethanolamine (lysoPE) species containing unsaturated fatty acids and free fatty acids were associated with an increased risk of CAD, whereas species of lysoPC and lyso-alkyl PC containing saturated fatty acids were associated with a decreased risk. Additionally, PC species containing palmitic acid, diacylglycerol, sphingomyelin, and ceramide were associated with an increased risk of MI, whereas PE-plasmalogen and phosphatidylinositol species were associated with a decreased risk. In MI patients, we found strong positive correlation between lipid metabolites related to the sphingolipid pathway, sphingomyelin, and ceramide and acute inflammatory markers (high-sensitivity C-reactive protein). The results of this study demonstrate altered signatures in lipid metabolism in patients with angina or MI. Lipidomic profiling could provide the information to identity the specific lipid metabolites under the presence of disturbed metabolic pathways in patients with CAD.
Highlights
Lipids are essential regulators of biological processes associated with normal cell function, metabolism, and distribution
When we subdivided the patients with coronary artery disease (CAD) into two groups according to treatment with lipid-lowering drugs (LLD), those not treated with LLD showed significantly higher serum concentrations of low-density lipoprotein (LDL) cholesterol than did those treated with LLD in both the angina and myocardial infarction (MI) groups (S2 Table)
Altered lipid metabolism associated with inflammation and oxidative stress is one of the primary drivers of the pathological changes associated with atherosclerotic plaque formation [8,9]
Summary
Lipids are essential regulators of biological processes associated with normal cell function, metabolism, and distribution. Changes in lipid components secondary to genetic alterations, environmental influences, or both can have profound effects on cell function, the immune system, and inflammatory responses [1,2]. These effects can cause various lipid dysregulationrelated diseases, including obesity [3], diabetes mellitus [4], and coronary artery disease (CAD) [5]. Previous studies demonstrated that endothelial dysfunction and increased oxidative stress are associated with the dysfunction and dysregulation of individual lipids. Impaired endothelial function has been linked to increased oxidative stress and altered lipid metabolism [10]. It is necessary to investigate the complex changes involved in lipid metabolism in CAD patients
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