Preferential sphingosine-1-phosphate enrichment and sphingomyelin depletion are key features of small dense HDL3 particles: relevance to antiapoptotic and antioxidative activities.

Abstract : OBJECTIVE: The purpose of this study was to define heterogeneity in the molecular profile of lipids, including sphingomyelin and sphingosine-1-phosphate, among physicochemically-defined HDL subpopulations and potential relevance to antiatherogenic biological activities of dense HDL3. METHODS AND RESULTS: The molecular profile of lipids (cholesteryl esters, phospholipids, sphingomyelin, and sphingosine-1-phosphate) in physicochemically-defined normolipidemic HDL subpopulations was determined by high-performance liquid chromatography and gas chromatography. As HDL particle size and molecular weight decreased with increment in density, molar lipid content diminished concomitantly. On a % basis, sphingomyelin abundance diminished in parallel with progressive increase in HDL density from HDL2b (12.8%) to HDL3c (6.2%; P<0.001); in contrast, sphingosine-1-phosphate was preferentially enriched in small HDL3 (40 to 50 mmol/mol HDL) versus large HDL2 (15 to 20 mmol/mol HDL; P<0.01). Small HDL3c was equally enriched in LpA-I particles relative to LpA-I:A-II. The sphingosine-1-phosphate/sphingomyelin ratio correlated positively with the capacities of HDL subspecies to attenuate apoptosis in endothelial cells (r=0.73, P<0.001) and to retard LDL oxidation (r=0.58, P<0.01). CONCLUSIONS: An elevated sphingosine-1-phosphate/sphingomyelin ratio is an integral feature of small dense HDL3, reflecting enrichment in sphingosine-1-phosphate, a key antiapoptotic molecule, and depletion of sphingomyelin, a structural lipid with negative impact on surface fluidity and LCAT activity. These findings further distinguish the structure and antiatherogenic activities of small, dense HDL.
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Article dans une revue
Arteriosclerosis, Thrombosis, and Vascular Biology, American Heart Association, 2007, 27 (8), pp.1843-9. 〈10.1161/ATVBAHA.107.145672〉
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http://www.hal.inserm.fr/inserm-00409657
Contributeur : Marie Francoise Simon <>
Soumis le : mardi 11 août 2009 - 14:41:25
Dernière modification le : mercredi 21 mars 2018 - 18:57:25

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Anatol Kontush, Patrice Therond, Amal Zerrad, Martine Couturier, Anne Nègre-Salvayre, et al.. Preferential sphingosine-1-phosphate enrichment and sphingomyelin depletion are key features of small dense HDL3 particles: relevance to antiapoptotic and antioxidative activities.. Arteriosclerosis, Thrombosis, and Vascular Biology, American Heart Association, 2007, 27 (8), pp.1843-9. 〈10.1161/ATVBAHA.107.145672〉. 〈inserm-00409657〉

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