Cholesterol efflux potential of sera from mice expressing human cholesteryl ester transfer protein and/or human apolipoprotein AI.
Cholesterol efflux potential of sera from mice expressing human cholesteryl ester transfer protein and/or human apolipoprotein AI.
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DOI：
10.1172/jci118326
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发表时间：
1995-12
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影响因子：
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通讯作者：
V. Atger;M. Moyà;M. Bamberger;O. Francone;P. Cosgrove;A. Tall;A. Walsh;N. Moatti;G. Rothblat
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文献类型：
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作者：
V. Atger;M. Moyà;M. Bamberger;O. Francone;P. Cosgrove;A. Tall;A. Walsh;N. Moatti;G. Rothblat
先前已经研究了全血清促进细胞胆固醇流出的能力以及人血清流出的载脂蛋白和脂蛋白组分之间的关系（de la Llera莫亚，M.，V. Atger，J.L. Paul，N. Fournier，N. Moatti，P. Giral，K.E.星期五，G.H.罗斯布拉特1994. Arterioscler. Thromb. 14：1056-1065）。我们现在已经使用这个实验系统来研究两个人类脂蛋白相关蛋白，载脂蛋白AI（载脂蛋白AI）和胆固醇酯转移蛋白（CETP）对细胞胆固醇流出的选择性影响，当这些蛋白质在转基因小鼠中表达。在4小时内从Fu 5AH供体细胞释放到来自不同组小鼠的5%血清的胆固醇的流出百分比值的顺序为：背景=人apo AI转基因（HuAITg）>人CETP转基因（HuCETPTg）>人apo AI和CETP转基因（HuAICETPTg）>> apo AI敲除小鼠。在每组小鼠中，发现外排和HDL胆固醇浓度之间存在强烈的正相关性（r2范围为0.64至0.76）。这些回归线的斜率在各组小鼠之间不同，表明血清的胆固醇受体效率在各组之间不同。这些相对效率的差异可以解释为什么胆固醇流出与各组小鼠中不同的HDL水平不成比例。我们可以得出结论：（a）来自HuAITg小鼠的HDL颗粒作为胆固醇受体的效率低于来自背景小鼠的HDL;（B）尽管由于较低的HDL胆固醇浓度导致较低的平均流出，但HDL颗粒在HuCETPTg小鼠中比在背景小鼠中更有效;和（c）与HuAITg小鼠相比，人apo AI和CETP的共表达提高了HuAICETPTg小鼠中HDL颗粒的效率。我们还证明，在HuAITg和AI敲除小鼠中，血清中卵磷脂胆固醇酰基转移酶从细胞释放的游离胆固醇的酯化作用降低，而在表达人CETP的两组小鼠中，它与背景值没有差异。
The ability of whole serum to promote cell cholesterol efflux and the relationships between apoprotein and lipoprotein components of human serum efflux have been investigated previously (de la Llera Moya, M., V. Atger, J.L. Paul, N. Fournier, N. Moatti, P. Giral, K.E. Friday, and G.H. Rothblat. 1994. Arterioscler. Thromb. 14:1056-1065). We have now used this experimental system to study the selective effects of two human lipoprotein-related proteins, apoprotein AI (apo AI) and cholesteryl ester transfer protein (CETP) on cell cholesterol efflux, when these proteins are expressed in transgenic mice. The percent efflux values for cholesterol released in 4 h from Fu5AH donor cells to 5% sera from the different groups of mice were in the order: background = human apo AI transgenic (HuAITg) > human CETP transgenic (HuCETPTg) > human apo AI and CETP transgenic (HuAICETPTg) >> apo AI knockout mice. In each group of mice a strong, positive correlation (r2 ranging from 0.64 to 0.76) was found between efflux and HDL cholesterol concentrations. The slopes of these regression lines differed between groups of mice, indicating that the cholesterol acceptor efficiencies of the sera differed among groups. These differences in relative efficiencies can explain why cholesterol efflux was not proportional to the different HDL levels in the various groups of mice. We can conclude that: (a) HDL particles from HuAITg mice are less efficient as cholesterol acceptors than HDL from the background mice; (b) despite a lower average efflux due to lower HDL cholesterol concentrations, HDL particles are more efficient in the HuCETPTg mice than in the background mice; and (c) the coexpression of both human apo AI and CETP improves the efficiency of HDL particles in the HuAICETPTg mice when compared with the HuAITg mice. We also demonstrated that the esterification of the free cholesterol released from the cells by lecithin cholesterol acyltransferase in the serum was reduced in the HuAITg and AI knockout mice, whereas it was not different from background values in the two groups of mice expressing human CETP.