抄録
It is well known that elevated plasma levels of low density lipoproteins (LDLs) are atherogenic. Recent advances in investigations on metabolism of lipoproteins by the artery wall with regard to uptake of LDL by macrophages resulting in fatty streak formation have yielded new insights into the factors involved in the arterial responses. A large amount of studies, in vitro and in vivo, supports the hypothesis that LDLs undergoing oxidative modifications are metabolized through a specific receptor, the acetyl LDL or scavenger receptor, on macrophages in arterial walls. In addition, it has been reported that some species of modified LDLs such as glycated LDL and malondialdehyde (MDA) -rich LDL probably exist in circulation. Then, the present study was undertaken to characterize MDA-LDL and their heterogeneity as a model of modified LDL, as compared with native LDL occurring in healthy and disease blood samples. MDA-LDL was produced by MDA and CuCl_2 reacted with normal LDL (n-LDL) (MDA-LDL_M and MDA-LDL_<Cu>, repectiveiy) in vitro. The LDL from uremics was enrolled in the study as a native modified LDL (MDA-LDL_<HD>). By elution through a gradient ion-exchange chromatography, the peak of MDA rich fraction (MRF) was separated at higher ionic strength, as compared with MDA poor fraction (MPF). The MPF was largest in MDA-LDL, especially MDA-LDL_<Cu>. The MDA-LDL_<Cu> showed fractions with most cathodal mobility on the agarose electrophoretic patterns, while MDA-LDL_M and MDA-LDL_<HD> had fractions with slightly cathodal mobility, as compared with n-LDL. Apolipoprotein (apo) B-100 in the MRF of n-LDL and MDA-LDL_<HD> showed electrophoretically an appearance of high molecular weight fractions, which also increased in MDA-LDL_M with additionally increasing amounts of MDA. Whereas, electrophoretic patterns in apo B-100 in MDA-LDL_<Cu> showed a number of the bands with low molecular weight fractions. From the findings, MDA-LDL_M is thought to be a model of modified LDL existing in native samples, since chemical characteristics are found to be similar between MDA-LDL_M and LDL_<HD>.
