Journal Article

Untargeted Mass Spectrometry Lipidomics identifies correlation between serum sphingomyelins and plasma cholesterol

Layal Abi Farraj, Pierre Zalloua, Jeremy K. Nicholson, Essa Hariri, Mark Lathrop, Francois Brial, David Touboul, Aurélie Le Lay, Justine Dubus, Dominique Gauguier, Alexandre Colleu, Hanane Kadar, Lyamine Hedjazi, Fumihiko Matsuda, Marc-Emmanuel Dumas

2019

Overview

Background Lipoproteins are major players in the development and progression of atherosclerotic plaques leading to coronary stenosis and myocardial infarction. Epidemiological, genetic and experimental observations have implicated the association of sphingolipids and intermediates of sphingolipid synthesis in atherosclerosis. We aimed to investigate relationships between quantitative changes in serum sphingolipids, the regulation of the metabolism of lipoproteins (LDL, HDL), and endophenotypes of coronary artery disease (CAD). Methods We carried out untargeted liquid chromatography – mass spectrometry (UPLC-MS) lipidomics of serum samples of subjects belonging to a cross-sectional study and recruited on the basis of absence or presence of angiographically-defined CAD, and extensively characterized for clinical and biochemical phenotypes. Results Among the 2998 spectral features detected in the serum samples, 1328 metabolic features were significantly correlated with at least one of the clinical or biochemical phenotypes measured in the cohort. We found evidence of significant associations between 34 metabolite signals, corresponding to a set of sphingomyelins, and serum HDL cholesterol. Many of these metabolite associations were also observed with serum LDL and total cholesterol levels but not as much with serum triglycerides. Conclusion Among patients with CAD, sphingolipids in the form of sphingomyelins are directly correlated with serum levels of lipoproteins and total cholesterol. Results from this study support the fundamental role of sphingolipids in modulating lipid serum levels, highlighting the importance to identify novel targets in the sphingolipid metabolic pathway for anti-atherogenic therapies.

• Publisher: Springer Science and Business Media LLC,BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: 0899 Other Information And Computing Sciences / 1101 Medical Biochemistry And Metabolomics / [CHIM.ANAL] Chemical Sciences/Analytical chemistry / [CHIM.CHEM]Chemical Sciences/Cheminformatics / [CHIM.OTHE]Chemical Sciences/Other / [CHIM.THEO] Chemical Sciences/Theoretical and/or physical chemistry / [CHIM]Chemical Sciences / [SDE.BE] Environmental Sciences/Biodiversity and Ecology / [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM] / [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism / [SDV.TOX.ECO] Life Sciences [q-bio]/Toxicology/Ecotoxicology / [SDV]Life Sciences [q-bio] / Adolescent / Adult / Aged / Aged, 80 and over / Analytical chemistry / Arteriosclerosis / ARTERY-DISEASE / Atherosclerosis / Biochemistry / Biochemistry & Molecular Biology / Biodiversity and Ecology / Biomarkers / Biomedical and Life Sciences / Blood cholesterol / Blood lipids / Cardiovascular disease / Chemical Sciences / Cholesterol / Cholesterol - blood / Chromatography / Clinical Nutrition / Coronary artery / Coronary Artery Disease / Coronary Artery Disease - blood / Coronary vessels / CORONARY-HEART-DISEASE / Development and progression / Ecotoxicology / Endocrinology and metabolism / Environmental Sciences / Epidemiology / Female / Gas Chromatography-Mass Spectrometry / Genetic aspects / HDL cholesterol / Heart attack / Heart diseases / High density lipoprotein / Human health and pathology / Humans / Hypertension / Identification / Intermediates / LARGE-SCALE / Life Sciences / Life Sciences & Biomedicine / Lipidology / Lipidomics / Lipids / Lipoproteins / Lipoproteins, HDL / Lipoproteins, HDL - blood / Lipoproteins, LDL / Lipoproteins, LDL - blood / Liquid chromatography / Low density lipoprotein / Low density lipoproteins / Male / Mass Spectrometry / Mass spectroscopy / Medical Biochemistry / Medical imaging / Medical research / Membrane lipids / METABOLISM / Metabolites / Metabolomics / Metabolomics - instrumentation / Metabolomics - methods / Middle Aged / Myocardial infarction / Novels / Nutrition & Dietetics / Nutritional diseases. Deficiency diseases / or physical chemistry / Phenotypes / Plant lipids / Plaques / RC620-627 / RISK-FACTOR / Science & Technology / Scientific imaging / Serum levels / Spectroscopy / Sphingolipids / Sphingomyelins / Sphingomyelins - blood / Stenosis / Theoretical and / TOXICITY / Toxicology / Triglycerides / UPLC-MS / Young Adult