Preferential Sphingosine-1-Phosphate Enrichment and Sphingomyelin Depletion Are Key Features of Small Dense HDL3 Particles

DOI Web Site 被引用文献5件
  • Anatol Kontush
    From the Université Pierre et Marie Curie-Paris 6 (A.K., J.A.d.S., S.C., M.J.C.), Paris; AP-HP, Groupe hospitalier Pitié-Salpétrière (A.K., J.A.d.S., S.C., M.J.C.), Paris; INSERM, Dyslipoproteinemia and Atherosclerosis Research Unit 551 (A.K., P.T., A.Z., M.C., A.N.-S., J.A.d.S., S.C., M.J.C.), Paris; Université Paris Descartes, Department of Biochemistry (P.T., A.Z., M.C.), EA 3617, Paris; and INSERM Unit 466 (A.N.-S.), CHU Rangueil, Toulouse, France.
  • Patrice Therond
    From the Université Pierre et Marie Curie-Paris 6 (A.K., J.A.d.S., S.C., M.J.C.), Paris; AP-HP, Groupe hospitalier Pitié-Salpétrière (A.K., J.A.d.S., S.C., M.J.C.), Paris; INSERM, Dyslipoproteinemia and Atherosclerosis Research Unit 551 (A.K., P.T., A.Z., M.C., A.N.-S., J.A.d.S., S.C., M.J.C.), Paris; Université Paris Descartes, Department of Biochemistry (P.T., A.Z., M.C.), EA 3617, Paris; and INSERM Unit 466 (A.N.-S.), CHU Rangueil, Toulouse, France.
  • Amal Zerrad
    From the Université Pierre et Marie Curie-Paris 6 (A.K., J.A.d.S., S.C., M.J.C.), Paris; AP-HP, Groupe hospitalier Pitié-Salpétrière (A.K., J.A.d.S., S.C., M.J.C.), Paris; INSERM, Dyslipoproteinemia and Atherosclerosis Research Unit 551 (A.K., P.T., A.Z., M.C., A.N.-S., J.A.d.S., S.C., M.J.C.), Paris; Université Paris Descartes, Department of Biochemistry (P.T., A.Z., M.C.), EA 3617, Paris; and INSERM Unit 466 (A.N.-S.), CHU Rangueil, Toulouse, France.
  • Martine Couturier
    From the Université Pierre et Marie Curie-Paris 6 (A.K., J.A.d.S., S.C., M.J.C.), Paris; AP-HP, Groupe hospitalier Pitié-Salpétrière (A.K., J.A.d.S., S.C., M.J.C.), Paris; INSERM, Dyslipoproteinemia and Atherosclerosis Research Unit 551 (A.K., P.T., A.Z., M.C., A.N.-S., J.A.d.S., S.C., M.J.C.), Paris; Université Paris Descartes, Department of Biochemistry (P.T., A.Z., M.C.), EA 3617, Paris; and INSERM Unit 466 (A.N.-S.), CHU Rangueil, Toulouse, France.
  • Anne Négre-Salvayre
    From the Université Pierre et Marie Curie-Paris 6 (A.K., J.A.d.S., S.C., M.J.C.), Paris; AP-HP, Groupe hospitalier Pitié-Salpétrière (A.K., J.A.d.S., S.C., M.J.C.), Paris; INSERM, Dyslipoproteinemia and Atherosclerosis Research Unit 551 (A.K., P.T., A.Z., M.C., A.N.-S., J.A.d.S., S.C., M.J.C.), Paris; Université Paris Descartes, Department of Biochemistry (P.T., A.Z., M.C.), EA 3617, Paris; and INSERM Unit 466 (A.N.-S.), CHU Rangueil, Toulouse, France.
  • Juliana A. de Souza
    From the Université Pierre et Marie Curie-Paris 6 (A.K., J.A.d.S., S.C., M.J.C.), Paris; AP-HP, Groupe hospitalier Pitié-Salpétrière (A.K., J.A.d.S., S.C., M.J.C.), Paris; INSERM, Dyslipoproteinemia and Atherosclerosis Research Unit 551 (A.K., P.T., A.Z., M.C., A.N.-S., J.A.d.S., S.C., M.J.C.), Paris; Université Paris Descartes, Department of Biochemistry (P.T., A.Z., M.C.), EA 3617, Paris; and INSERM Unit 466 (A.N.-S.), CHU Rangueil, Toulouse, France.
  • Sandrine Chantepie
    From the Université Pierre et Marie Curie-Paris 6 (A.K., J.A.d.S., S.C., M.J.C.), Paris; AP-HP, Groupe hospitalier Pitié-Salpétrière (A.K., J.A.d.S., S.C., M.J.C.), Paris; INSERM, Dyslipoproteinemia and Atherosclerosis Research Unit 551 (A.K., P.T., A.Z., M.C., A.N.-S., J.A.d.S., S.C., M.J.C.), Paris; Université Paris Descartes, Department of Biochemistry (P.T., A.Z., M.C.), EA 3617, Paris; and INSERM Unit 466 (A.N.-S.), CHU Rangueil, Toulouse, France.
  • M. John Chapman
    From the Université Pierre et Marie Curie-Paris 6 (A.K., J.A.d.S., S.C., M.J.C.), Paris; AP-HP, Groupe hospitalier Pitié-Salpétrière (A.K., J.A.d.S., S.C., M.J.C.), Paris; INSERM, Dyslipoproteinemia and Atherosclerosis Research Unit 551 (A.K., P.T., A.Z., M.C., A.N.-S., J.A.d.S., S.C., M.J.C.), Paris; Université Paris Descartes, Department of Biochemistry (P.T., A.Z., M.C.), EA 3617, Paris; and INSERM Unit 466 (A.N.-S.), CHU Rangueil, Toulouse, France.

書誌事項

タイトル別名
  • Relevance to Antiapoptotic and Antioxidative Activities

説明

<jats:p> <jats:bold> <jats:italic>Objective—</jats:italic> </jats:bold> 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. </jats:p> <jats:p> <jats:bold> <jats:italic>Methods and Results—</jats:italic> </jats:bold> 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%; <jats:italic>P</jats:italic> <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; <jats:italic>P</jats:italic> <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 ( <jats:italic>r</jats:italic> =0.73, <jats:italic>P</jats:italic> <0.001) and to retard LDL oxidation ( <jats:italic>r</jats:italic> =0.58, <jats:italic>P</jats:italic> <0.01). </jats:p> <jats:p> <jats:bold> <jats:italic>Conclusions—</jats:italic> </jats:bold> 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. </jats:p>

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