CETP-deficient patients carry two distinct LDL particle species in every density subfraction, suggesting a second LDL formation pathway (Arterioscler Thromb 1991)

By equilibrium density gradient ultracentrifugation, we analyzed the chemical composition and particle size of low density lipoproteins (LDLs) in 16 subfractions separated from the LDL fractions (1.019 less than d less than 1.063 g/ml) of two hyperalphalipoproteinemic patients who had a deficiency of cholesteryl ester transfer protein (CETP). The LDLs of these patients comprised a group of heterogeneous lipoprotein particles distributed almost equally in a wide density range from d = 1.025 g/ml to d = 1.053 g/ml, whereas LDLs from normal controls were a homogeneous group of lipoprotein particles distributed in a narrow density range from d = 1.030 g/ml to d = 1.046 g/ml. The LDL in each subfraction derived from the patients' plasma samples was poor in cholesteryl ester and rich in triglycerides and apolipoproteins. Each subfraction of normal control LDL contained only one species of homogeneous LDL particles, which progressively decreased in size with an increase in the density of the fraction. In contrast, each subfraction of patient LDL contained two species of LDL particles: smaller LDLs existed, in addition to those that were found to be identical to the normal control LDL particles observed in the corresponding subfractions. The intermediate density lipoproteins of the two patients were also composed of two species of lipoproteins. From these results, we speculate that two metabolic pathways may exist in the LDL formation process. In this process, the transfer of cholesteryl ester from high density lipoproteins by CETP may convert the smaller lipoprotein particles to the larger ones, forming the homogeneous LDL species.