Small, Dense High-Density Lipoprotein-3 Particles Are Enriched in Negatively Charged Phospholipids Relevance to Cellular Cholesterol Efflux, Antioxidative, Antithrombotic, Anti-Inflammatory, and Antiapoptotic Functionalities
Small, Dense High-Density Lipoprotein-3 Particles Are Enriched in Negatively Charged Phospholipids Relevance to Cellular Cholesterol Efflux, Antioxidative, Antithrombotic, Anti-Inflammatory, and Antiapoptotic Functionalities
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DOI：
10.1161/atvbaha.113.301468
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发表时间：
2013-12-01
影响因子：
8.7
通讯作者：
Kontush, Anatol
中科院分区：
文献类型：
--
作者：
Camont, Laurent;Lhomme, Marie;Kontush, Anatol
目的高密度脂蛋白（HDL）具有多种抗动脉粥样硬化作用，其结构、组成和功能具有高度异质性，其抗动脉粥样硬化作用的分子决定因素尚不完全清楚。由于磷脂代表HDL的主要生物活性脂质组分，我们表征了主要正常血脂HDL亚群的磷脂酰鞘脂组，并将其与HDL functional.Approach和结果使用用于磷脂和鞘脂分析的原始液相色谱-质谱/质谱方法，在9个脂质亚类中定量了162种单独的分子脂质种类，磷脂酰胆碱>鞘磷脂>溶血磷脂酰胆碱>磷脂酰乙醇胺>磷脂酰肌醇>神经酰胺>磷脂酰丝氨酸>磷脂酰甘油>磷脂酸。当数据表示相对于总脂质，溶血磷脂酰胆碱和带负电荷的磷脂酰丝氨酸和磷脂酸的含量随着HDL的水合密度的增加而逐渐增加，而鞘磷脂和神经酰胺的比例下降。HDL亚群的关键生物学活性，特别是人THP-1巨噬细胞的胆固醇流出能力、对低密度脂蛋白氧化的抗氧化活性、人血小板中的抗血栓形成活性、无细胞抗炎活性和内皮细胞中的抗凋亡活性，主要与小的、致密的、富含蛋白的HDL 3相关。高密度脂蛋白颗粒的生物活性强烈的相互关联，表现出显着的相关性与多个组件的高密度脂蛋白磷酸鞘脂。磷脂酰丝氨酸的含量与HDL功能的所有指标呈正相关，反映了磷脂酰丝氨酸在小而致密的HDL 3中的富集。结论HDL脂质体的结构-功能分析表明，HDL脂质体可能强烈影响其抗动脉粥样硬化的功能。
Objective High-density lipoprotein (HDL) displays multiple atheroprotective activities and is highly heterogeneous in structure, composition, and function; the molecular determinants of atheroprotective functions of HDL are incompletely understood. Because phospholipids represent a major bioactive lipid component of HDL, we characterized the phosphosphingolipidome of major normolipidemic HDL subpopulations and related it to HDL functionality.Approach and Results Using an original liquid chromatography-mass spectrometry/mass spectrometry methodology for phospholipid and sphingolipid profiling, 162 individual molecular lipid species were quantified across the 9 lipid subclasses, in the order of decreasing abundance, phosphatidylcholine>sphingomyelin>lysophosphatidylcholine>phosphatidylethanolamine>phosphatidylinositol>ceramide>phosphatidylserine>phosphatidylglycerol>phosphatidic acid. When data were expressed relative to total lipid, the contents of lysophosphatidylcholine and of negatively charged phosphatidylserine and phosphatidic acid increased progressively with increase in hydrated density of HDL, whereas the proportions of sphingomyelin and ceramide decreased. Key biological activities of HDL subpopulations, notably cholesterol efflux capacity from human THP-1 macrophages, antioxidative activity toward low-density lipoprotein oxidation, antithrombotic activity in human platelets, cell-free anti-inflammatory activity, and antiapoptotic activity in endothelial cells, were predominantly associated with small, dense, protein-rich HDL3. The biological activities of HDL particles were strongly intercorrelated, exhibiting significant correlations with multiple components of the HDL phosphosphingolipidome. Specifically, the content of phosphatidylserine revealed positive correlations with all metrics of HDL functionality, reflecting enrichment of phosphatidylserine in small, dense HDL3.Conclusions Our structure-function analysis thereby reveals that the HDL lipidome may strongly affect atheroprotective functionality.