Determination of the lower threshold of apolipoprotein E resulting in remnant lipoprotein clearance.
Determination of the lower threshold of apolipoprotein E resulting in remnant lipoprotein clearance.
复制标题
DOI：
--
复制
发表时间：
1999-08
影响因子：
6.5
通讯作者：
A. Hasty;M. Linton;L. Swift;S. Fazio
中科院分区：
文献类型：
--
作者：
A. Hasty;M. Linton;L. Swift;S. Fazio
载脂蛋白 E (apoE) 是受体介导的残余脂蛋白清除的配体。通过将野生型骨髓移植到 apoE(-/-) 小鼠体内，ApoE 浓度仅为正常浓度的 10%，足以维持正常的血清脂质和脂蛋白水平。本研究的目的是确定仍然影响胆固醇水平的血清 apoE 的最小浓度，并确定是否可以检测到低于该 apoE 水平对残余物清除的任何影响。将ApoE(+/+)骨髓与apoE(-/-)骨髓按1%、5%、10%和25%混合，制成嵌合小鼠，其血清apoE水平为0.005至0.46mg/dl。血清胆固醇和 apoE 水平的分析表明，apoE 水平与胆固醇降低呈正相关 (r = 0.83)，0.04 mg/dl 的水平代表功能阈值水平。通过 FPLC、非变性凝胶电泳和周转研究评估，apoE(-/-) 小鼠和血清 apoE 低于 0.04 mg/dl 的小鼠之间的脂蛋白谱和清除率没有差异。然而，负染色的电子显微镜显示，与apoE(-/-)小鼠相比，这些小鼠血清中直径<30 nm的脂蛋白颗粒较少。这些数据表明，导致胆固醇降低的血清apoE的阈值是0. 04 mg/dl，并且表明低于该水平的apoE可能通过加速较小残余物的清除来影响脂蛋白大小分布。
Apolipoprotein E (apoE) is the ligand for receptor-mediated clearance of remnant lipoproteins. ApoE at concentrations only 10% of normal, achieved through transplantation of wild-type marrow into apoE(-/-) mice, is sufficient for the maintenance of normal serum lipid and lipoprotein levels. The goal of the present study was to identify the minimal concentration of serum apoE still affecting cholesterol levels, and to determine whether any effects on remnant clearance below this level of apoE were detectable. ApoE(+/+) marrow was mixed with apoE(-/-) marrow in proportions of 1, 5, 10, and 25% to make chimeric mice with serum levels of apoE ranging from 0.005 to 0.46 mg/dl. Analysis of serum cholesterol and apoE levels demonstrated a positive correlation between apoE levels and cholesterol reduction (r = 0.83), with levels of 0.04 mg/dl representing the functional threshold level. There were no differences in lipoprotein profiles and clearance between apoE(-/-) mice and mice with serum apoE of less than 0.04 mg/dl, as assessed by FPLC, non-denaturing gel electrophoresis, and turnover studies. However, electron microscopy of negative stains showed fewer lipoprotein particles with a diameter of <30 nm in the serum of these mice compared to apoE(-/-) mice. These data demonstrate that the threshold of serum apoE resulting in cholesterol reduction is 0. 04 mg/dl, and indicate that apoE below this level affects lipoprotein size distribution possibly by accelerating the clearance of smaller remnants.