HDL stimulates the efflux of peroxidized phospholipids from foam cells and its visualization

动脉粥样硬化是冠状动脉疾病和脑血管疾病的潜在过程，是工业化国家发病率的主要原因。以预防动脉粥样硬化为目的，人们对动脉粥样硬化的发生机制以及膳食成分对动脉粥样硬化的保护作用进行了广泛的研究。在此，我们首次证明了作为动脉粥样硬化主要原因的高脂血症患者血浆中磷脂酰胆碱氢过氧化物（PCOOH，位于血浆脂蛋白颗粒表面的磷脂酰胆碱的主要氧化产物）的水平明显高于健康志愿者。这表明高脂血症患者具有大量的最低氧化脂蛋白，并暗示脂蛋白磷脂的过氧化对动脉粥样硬化病变的形成尤为重要。在使用人单核细胞系（THP-1）的情况下，巨噬细胞样THP-1细胞有效吞噬富含PCOOH的氧化低密度脂蛋白（oxLDL），导致PCOOH在细胞中明显积累。通过在氧化ldl处理的THP-1细胞中添加高密度脂蛋白（HDL），细胞PCOOH有效减弱。因此，我们研究了PCOOH从oxLDL到HDL的掺入机制，并通过体外细胞培养实验和超灵敏LC-MS分析证实了HDL降低PCOOH的能力。另一方面，荧光标记的PCOOH能够在实验中制备，并研究这种PCOOH的可视化（即荧光监测oxLDL进入THP-1细胞）。本研究证实HDL通过降低PCOOH显示抗氧化功能。

Atherosclerosis is the process underlying coronary artery disease and cerebrovascular disease, and is a leading cause of morbidity in industrialized countries. With the aim of atherosclerosis prevention, mechanisms of atherosclerosis development as well as its protection by dietary food components have been studied worldwide. Here, we demonstrated for the first time that in patient with hyperlipidemia as a major cause of atherosclerosis, the levels of plasma phosphatidylcholine hydroperoxide (PCOOH; that is a primary oxidation product of phosphatidylcholine which located on the surface of plasma lipoprotein particle) were significantly higher than in the healthy volunteers. This indicated that hyperlipidemic patients possess a substantial amount of minimally-oxidized lipoproteins, and implied that the peroxidation of lipoprotein phospholipids would be especially important for the atherosclerotic lesion formation. In the case for using the human monocyte cell line (THP-1), macrophage-like THP-1 cells effectively phagocytized PCOOH-riched oxidized low density lipoprotein (oxLDL), which resulted in the marked accumulation of PCOOH in the cells. By the addition of high density lipoprotein (HDL) to the oxLDL-treated THP-1 cells, cellular PCOOH efficiently attenuated. Thus, we investigated the incorporation mechanism of PCOOH from oxLDL to HDL, and confirmed the ability of HDL to reduce PCOOH by in vitro cell culture experiments and ultra-sensitive LC-MS analysis. On the other hand, fluorescence-labeled PCOOH was able to prepare experimently, and investigated visualization of such PCOOH (I.e., fluorometrically monitorization of the incorporation of oxLDL into THP-1 cells). The present study confirmed that HDL revealed antioxidative function via the reduction of PCOOH.