Preferential sphingosine-1-phosphate enrichment and sphingomyelin depletion are key features of small dense HDL3 particles -: Relevance to antiapoptotic and antioxidative activities
Preferential sphingosine-1-phosphate enrichment and sphingomyelin depletion are key features of small dense HDL3 particles -: Relevance to antiapoptotic and antioxidative activities
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DOI：
10.1161/atvbaha.107.145672
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发表时间：
2007-08-01
影响因子：
8.7
通讯作者：
Chapman, M. John
中科院分区：
文献类型：
--
作者：
Kontush, Anatol;Therond, Patrice;Chapman, M. John
目的：本研究的目的是确定物理化学定义的高密度脂蛋白亚群中脂类(包括鞘磷脂和1-磷酸鞘氨醇)分子谱的异质性及其与致密高密度脂蛋白抗动脉粥样硬化生物活性的潜在相关性。方法和结果-用高效液相和气相色谱测定了物理化学定义的降脂高密度脂蛋白亚群中脂类(胆固醇酯、磷脂、鞘磷脂和1-磷酸鞘氨醇)的分子谱。随着密度的增加，高密度脂蛋白的颗粒尺寸和相对分子质量减小，摩尔脂含量也随之降低。从高密度脂蛋白2b(12.8%)到高密度脂蛋白3c(6.2%；P&0.001)，神经鞘磷脂的丰度随着高密度脂蛋白密度的递增而减少；相反，1-磷酸鞘氨醇优先在小高密度脂蛋白(40-50mmolHDL3)中富含，而在大高密度脂蛋白(15-20mmolHDL0.01)中优先富含。相对于LPA-I：A-II，较小的HDL3c在LPA-I：A-II颗粒中的丰度相同。1-磷酸鞘氨醇/鞘磷脂比值与高密度脂蛋白亚种抑制内皮细胞凋亡和延缓低密度脂蛋白氧化的能力呈正相关(r=0.001.73，P=0.58，P=0.0 1)。结论：1-磷酸鞘氨醇/鞘磷脂比值升高是小密度高密度脂蛋白的一个重要特征，反映了关键的抗细胞凋亡分子1-磷酸鞘氨醇的丰富和对表面流动性和LCAT活性有负面影响的结构性脂质鞘磷脂的减少。这些发现进一步区分了小而致密的高密度脂蛋白的结构和抗动脉粥样硬化活性。
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.