ABNORMAL INVIVO METABOLISM OF APOLIPOPROTEIN-E4 IN HUMANS
ABNORMAL INVIVO METABOLISM OF APOLIPOPROTEIN-E4 IN HUMANS
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DOI：
10.1172/jci112645
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发表时间：
1986-09-01
影响因子：
15.9
通讯作者：
BREWER, HB
中科院分区：
文献类型：
--
作者：
GREGG, RE;ZECH, LA;BREWER, HB
载脂蛋白E（apoE）在调节富含脂蛋白酰亚胺的脂蛋白颗粒的残余物的代谢中是重要的。它是一种多态性蛋白，具有编码apoE 2、apoE 3和apoE 4的三种常见等位基因。ApoE 3被认为是正常的同种型，而apoE 4与高胆固醇血症和V型高脂蛋白血症两者相关。我们定量分析了19例正常血脂apoE 3纯合子和1例正常血脂apoE 4纯合子的apoE 4代谢动力学，并与12例正常血脂apoE 3纯合子的apoE 3代谢动力学进行了比较。在apoE 3纯合受试者中，apoE 4的分解代谢速度是apoE 3的两倍，平均血浆停留时间为0.37 ± 0.05。0.01 d（.+-. SEM）和0.73 . 0.05（P < 0.001）。当血浆被分馏成脂蛋白亚类，标记的载脂蛋白E4的最大量是本非常低密度脂蛋白，而标记的载脂蛋白E3的最大部分与高密度脂蛋白。与apoE 3纯合子相比，apoE 4纯合子的血浆apoE浓度降低（3.11 mg/dl vs.4.83 ±. 0.35 mg/dl）。apoE 4浓度的降低完全是由于apoE 4纯合子中apoE 4停留时间的降低（0.36天对0.73 ± 0.01天）。0.05 d为apoE 3纯合子中的apoE 3）。这些结果表明apoE 4与apoE 3在动力学上不同，并表明apoE 4在高胆固醇血症和V型高脂蛋白血症个体中的存在可能在这些异常脂蛋白血症的发生中发挥重要的病理生理作用。
Apolipoprotein E (apoE) is important in modulating the catabolism of remnants of triglyceride-rich lipoprotein particles. It is a polymorphic protein with the three common alleles coding for apoE2, apoE3, and apoE4. ApoE3 is considered the normal isoform, while apoE4 is associated both with hypercholesterolemia and type V hyperlipoproteinemia. We quantitated the kinetics of metabolism of apoE4 in 19 normolipidemic apoE3 homozygotes and 1 normolipidemic apoE4 homozygote, and compared this with the metabolism of apoE3 in 12 normolipidemic apoE3 homozygotes. In the apoE3 homozygous subjects, apoE4 was catabolized twice as fast as apoE3, with a mean plasma residence time of 0.37 .+-. 0.01 d (.+-.SEM) and 0.73 .+-. 0.05 (P < 0.001), respectively. When plasma was fractionated into the lipoprotein subclasses, the greatest amount of labeled apoE4 was present on very low density lipoproteins, while the largest fraction of labeled apoE3 was associated with high density lipoproteins. The plasma apoE concentration was decreased in an apoE4 homozygote compared with the apoE3 homozygotes (3.11 mg/dl vs. 4.83 .+-. 0.35 mg/dl). The reduced apoE4 concentration was entirely due to a decreased apoE4 residence time in the apoE4 homozygote (0.36 d vs. 0.73 .+-. 0.05 d for apoE3 in apoE3 homozygotes). These results indicate that apoE4 is kinetically different than apoE3, and suggest that the presence of apoE4 in hypercholesterolemic and type V hyperlipoproteinemic individuals may play an important pathophysiological role in the development of these dyslipoproteinemias.