Ehnholm C, Mahley R W, Chappell D A, Weisgraber K H, Ludwig E, Witztum J L
Proc Natl Acad Sci U S A. 1984 Sep;81(17):5566-70. doi: 10.1073/pnas.81.17.5566.
The beta-very low density lipoproteins (beta-VLDL) that accumulate in type III hyperlipoproteinemic subjects can be divided into two fractions (fraction I and fraction II), which differ in size, lipid composition, and the type of apolipoprotein B (apo-B) present in the particles. The apo-B48-containing particles (fraction I) are of intestinal origin, while apo-B100-containing particles (fraction II) are derived from the liver. Both fractions contain a defective form of apo-E referred to as apo-E2. Intravenous infusion of heparin into two subjects with type III hyperlipoproteinemia resulted in the complete removal of fraction II particles from density less than 1.006 g/ml, while fraction I particles remained at this density. In vitro studies confirmed that fraction I particles did not change density when subjected to hydrolysis with lipoprotein lipase, while fraction II particles shifted to the intermediate density lipoprotein range (approximately equal to 1.02 g/ml). When the beta-VLDL were hydrolyzed by lipoprotein lipase in the presence of density greater than 1.21 g/ml lipoprotein-deficient plasma, the addition of normal apo-E (apo-E3), but not apo-E2, resulted in a shift of fraction II particles to the low density lipoprotein (LDL) range (approximately equal to 1.05 g/ml). Fraction I particles did not undergo a shift to this higher density, supporting previous observations that apo-B48-containing particles are not converted to LDL. The demonstration that apo-B100-containing particles in type III hyperlipoproteinemic subjects could be converted to particles with the density of LDL suggests that apo-E plays a role in the normal conversion of VLDL to LDL. The mutant form of apo-E (apo-E2) found in the beta-VLDL from type III hyperlipoproteinemic subjects appears to impede this conversion, whereas the addition of normal apo-E (apo-E3) allows the processing to occur.
在III型高脂蛋白血症患者体内蓄积的β-极低密度脂蛋白（β-VLDL）可分为两个组分（组分I和组分II），它们在大小、脂质组成以及颗粒中所含载脂蛋白B（apo-B）的类型方面存在差异。含apo-B48的颗粒（组分I）源自肠道，而含apo-B100的颗粒（组分II）源自肝脏。两个组分均含有一种缺陷形式的apo-E，称为apo-E2。对两名III型高脂蛋白血症患者静脉输注肝素，导致密度小于1.006 g/ml的组分II颗粒被完全清除，而组分I颗粒仍保留在该密度。体外研究证实，组分I颗粒在用脂蛋白脂肪酶水解时密度不变，而组分II颗粒则转移至中间密度脂蛋白范围（约等于1.02 g/ml）。当β-VLDL在密度大于1.21 g/ml的无脂蛋白血浆存在下被脂蛋白脂肪酶水解时，添加正常的apo-E（apo-E3）而非apo-E2会导致组分II颗粒转移至低密度脂蛋白（LDL）范围（约等于1.05 g/ml）。组分I颗粒未转移至这个更高密度，这支持了先前的观察结果，即含apo-B48的颗粒不会转化为LDL。III型高脂蛋白血症患者体内含apo-B100的颗粒可转化为具有LDL密度的颗粒，这一证明表明apo-E在VLDL正常转化为LDL过程中发挥作用。在III型高脂蛋白血症患者的β-VLDL中发现的apo-E突变形式（apo-E2）似乎阻碍了这种转化，而添加正常的apo-E（apo-E3）则能使这一过程发生。
