Emile Zakiev1, Fabiana Rached2, Marie Lhomme3, Maryam Darabi-Amin1, Maharajah Ponnaiah3, Pierre Hadrien Becker4, Patrice Therond4, Carlos V Serrano2, Raul D Santos5, M John Chapman1, Alexander Orekhov6, Anatol Kontush7. 1. UMR-ICAN 1166, National Institute for Health and Medical Research (INSERM), Sorbonne University, Paris, France. 2. Heart Institute (InCor), University of Sao Paulo Medical School Hospital, Sao Paulo, Brazil. 3. ICANalytics, Institute of Cardiometabolism and Nutrition (IHU-ICAN, ANR-10-IAHU-05), Paris, France. 4. Service de Biochimie, AP-HP, HUPS, Biochemistry Laboratory of Bicêtre Hospital, Le Kremlin-Bicêtre, France. 5. Heart Institute (InCor), University of Sao Paulo Medical School Hospital, Sao Paulo, Brazil; Preventive Medicine Center and Cardiology Program of Hospital Israelita Albert Einstein, Sao Paulo, Brazil. 6. Laboratory of Angiopathology, Institute of General Pathology and Pathophysiology, Moscow, Russia; Institute for Atherosclerosis Research, Skolkovo Innovative Centre, Moscow, Russia. 7. UMR-ICAN 1166, National Institute for Health and Medical Research (INSERM), Sorbonne University, Paris, France. Electronic address: anatol.kontush@upmc.fr.
Abstract
BACKGROUND: Familial apolipoprotein A-I (apoA-I) deficiency (FAID) involving low levels of both apoA-I and high-density lipoprotein (HDL) cholesterol is associated with accelerated atherosclerosis. OBJECTIVE: The objective of this study was to define distinctive patterns in the lipidome of HDL subpopulations in FAID in relationship to antiatherogenic activities. METHODS: Five HDL subfractions were isolated by ultracentrifugation from plasma of FAID Caucasian patients (n = 5) and age-matched healthy normolipidemic Caucasian controls (n = 8), and the HDL lipidome (160 molecular species of 9 classes of phospholipids and sphingolipids) was quantitatively evaluated. RESULTS: Increased concentrations of numerous molecular species of lysophosphatidylcholine (up to 12-fold), ceramides (up to 3-fold), phosphatidylserine (up to 34-fold), phosphatidic acid (up to 71-fold), and phosphatidylglycerol (up to 20-fold) were detected throughout all five HDL subpopulations as compared with their counterparts from controls, whereas concentrations of phosphatidylethanolamine species were decreased (up to 5-fold). Moderately to highly abundant, within their lipid class, species of phosphatidylcholine, sphingomyelin, phosphatidylinositol, phosphatidylethanolamine, phosphatidylserine, and ceramide featuring multiple unsaturations were primarily affected by apoA-I deficiency; their HDL content, particularly that of phosphatidylcholine (34:2), was strongly correlated with HDL function, impaired in FAID. Metabolic pathway analysis revealed that sphingolipid, glycerophospholipid, and linoleic acid metabolism was significantly affected by FAID. CONCLUSION: These data reveal that altered content of specific phospholipid and sphingolipid species is linked to deficient antiatherogenic properties of HDL in FAID.
BACKGROUND: Familial apolipoprotein A-I (apoA-I) deficiency (FAID) involving low levels of both apoA-I and high-density lipoprotein (HDL) cholesterol is associated with accelerated atherosclerosis. OBJECTIVE: The objective of this study was to define distinctive patterns in the lipidome of HDL subpopulations in FAID in relationship to antiatherogenic activities. METHODS: Five HDL subfractions were isolated by ultracentrifugation from plasma of FAID Caucasian patients (n = 5) and age-matched healthy normolipidemic Caucasian controls (n = 8), and the HDL lipidome (160 molecular species of 9 classes of phospholipids and sphingolipids) was quantitatively evaluated. RESULTS: Increased concentrations of numerous molecular species of lysophosphatidylcholine (up to 12-fold), ceramides (up to 3-fold), phosphatidylserine (up to 34-fold), phosphatidic acid (up to 71-fold), and phosphatidylglycerol (up to 20-fold) were detected throughout all five HDL subpopulations as compared with their counterparts from controls, whereas concentrations of phosphatidylethanolamine species were decreased (up to 5-fold). Moderately to highly abundant, within their lipid class, species of phosphatidylcholine, sphingomyelin, phosphatidylinositol, phosphatidylethanolamine, phosphatidylserine, and ceramide featuring multiple unsaturations were primarily affected by apoA-I deficiency; their HDL content, particularly that of phosphatidylcholine (34:2), was strongly correlated with HDL function, impaired in FAID. Metabolic pathway analysis revealed that sphingolipid, glycerophospholipid, and linoleic acid metabolism was significantly affected by FAID. CONCLUSION: These data reveal that altered content of specific phospholipid and sphingolipid species is linked to deficient antiatherogenic properties of HDL in FAID.
Authors: Sara Fernández-Castillejo; Anna Pedret; Úrsula Catalán; Rosa-Maria Valls; Marta Farràs; Laura Rubió; Olga Castañer; Alba Macià; Montse Fitó; Maria José Motilva; Maria-Isabel Covas; Martin Giera; Alan T Remaley; Rosa Solà Journal: Mol Nutr Food Res Date: 2021-03-18 Impact factor: 6.575