Gabelli C, Gregg R E, Zech L A, Manzato E, Brewer H B
J Lipid Res. 1986 Mar;27(3):326-33.
Apolipoprotein(apo) E deficiency is an inherited disease characterized by type III hyperlipoproteinemia and less than 1% normal plasma apoE concentration. The role of apoE in LDL metabolism was investigated by quantitating the metabolism of radiolabeled normal and apoE-deficient LDL in both normal and apoE-deficient subjects. ApoE deficiency resulted in an accumulation of plasma IDL, and a decreased synthesis of LDL consistent with a block in the conversion of IDL to LDL. The LDL isolated from the apoE-deficient patient was similar to normal LDL in hydrated density, size, and composition. However, the apoE-deficient LDL was kinetically abnormal with delayed catabolism in both normal subjects and the apoE-deficient patient. In addition, the catabolism of normal LDL in the apoE-deficient subject was increased. These results were interpreted as indicating that apoE is necessary for the conversion of IDL to LDL and the formation of kinetically normal LDL. The rapid catabolism of normal LDL in the apoE-deficient patient suggests an up-regulation of the hepatic LDL receptor pathway. Based on these results, apoE is proposed to play an important role in the conversion of IDL to LDL, the formation of kinetically normal LDL, and the regulation of LDL receptor function.
载脂蛋白（apo）E缺乏症是一种遗传性疾病，其特征为III型高脂蛋白血症且血浆apoE浓度低于正常水平的1%。通过对正常受试者和apoE缺乏症受试者体内放射性标记的正常LDL和apoE缺乏的LDL的代谢进行定量研究，探讨了apoE在LDL代谢中的作用。apoE缺乏导致血浆中间密度脂蛋白（IDL）蓄积，LDL合成减少，这与IDL向LDL转化受阻一致。从apoE缺乏症患者分离出的LDL在水合密度、大小和组成方面与正常LDL相似。然而，apoE缺乏的LDL在动力学上是异常的，在正常受试者和apoE缺乏症患者中其分解代谢均延迟。此外，apoE缺乏症受试者体内正常LDL的分解代谢增加。这些结果被解释为表明apoE对于IDL向LDL的转化以及动力学正常的LDL的形成是必需的。apoE缺乏症患者中正常LDL的快速分解代谢提示肝脏LDL受体途径上调。基于这些结果，提出apoE在IDL向LDL的转化、动力学正常的LDL的形成以及LDL受体功能的调节中起重要作用。
