OBJECTIVE To characterize the fate of protein and lipid in nascent HDL (high-density lipoprotein) in plasma and explore the role of interaction between nascent HDL and mature HDL in promoting ABCA1 (ATP-binding cassette transporter 1)-dependent cholesterol efflux. Approach and Results: Two discoidal species, nascent HDL produced by RAW264.7 cells expressing ABCA1 (LpA-I [apo AI containing particles formed by incubating ABCA1-expressing cells with apo AI]), and CSL112, human apo AI (apolipoprotein AI) reconstituted with phospholipids, were used for in vitro incubations with human plasma or purified spherical plasma HDL. Fluorescent labeling and biotinylation of HDL were employed to follow the redistribution of cholesterol and apo AI, cholesterol efflux was measured using cholesterol-loaded cells. We show that both nascent LpA-I and CSL112 can rapidly fuse with spherical HDL. Redistribution of the apo AI molecules and cholesterol after particle fusion leads to the formation of (1) enlarged, remodeled, lipid-rich HDL particles carrying lipid and apo AI from LpA-I and (2) lipid-poor apo AI particles carrying apo AI from both discs and spheres. The interaction of discs and spheres led to a greater than additive elevation of ABCA1-dependent cholesterol efflux. CONCLUSIONS These data demonstrate that although newly formed discs are relatively poor substrates for ABCA1, they can interact with spheres to produce lipid-poor apo AI, a much better substrate for ABCA1. Because the lipid-poor apo AI generated in this interaction can itself become discoid by the action of ABCA1, cycles of cholesterol efflux and disc-sphere fusion may result in net ABCA1-dependent transfer of cholesterol from cells to HDL spheres. This process may be of particular importance in atherosclerotic plaque where cholesterol acceptors may be limiting.

中文翻译：

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新生的HDL（高密度脂蛋白）光盘将胆固醇运送到HDL球体：HDL颗粒重塑对胆固醇外流的影响。

目的表征血浆新生HDL（高密度脂蛋白）中蛋白质和脂质的命运，并探讨新生HDL和成熟HDL之间的相互作用在促进ABCA1（ATP结合盒转运蛋白1）依赖性胆固醇外流中的作用。方法和结果：两个盘状物种，由表达ABCA1的RAW264.7细胞产生的新生HDL（LpA-I [含有通过表达abca1的细胞与apo AI一起孵育而形成的颗粒的apo AI]）和CSL112，人apo AI（载脂蛋白AI）用磷脂重构的脂质用于与人血浆或纯化的球形血浆HDL的体外温育。HDL的荧光标记和生物素化被用来追踪胆固醇和载脂蛋白AI的重新分布，使用载有胆固醇的细胞测量胆固醇外流。我们显示，新生的LpA-I和CSL112均可与球形HDL快速融合。颗粒融合后apo AI分子和胆固醇的重新分布导致形成（1）携带LpA-1携带脂质和apo AI的扩大，重塑的富含脂质的HDL颗粒，以及（2）携带apo AI的贫脂apo AI颗粒从圆盘和球体。椎间盘与球体的相互作用导致大于依赖于ABCA1的胆固醇外排的增加。结论这些数据表明，尽管新形成的椎间盘是ABCA1的相对较差的底物，但它们可以与球体相互作用以产生贫脂的apo AI，ABCA1的底物要好得多。由于在这种相互作用中产生的贫脂apo AI本身可以通过ABCA1的作用变成盘状，胆固醇外排和椎间盘球融合的周期可能导致胆固醇从细胞到HDL球的净ABCA1依赖性转移。该过程在胆固醇受体可能受到限制的动脉粥样硬化斑块中可能特别重要。