[Serum lipoprotein and atherogenicity--relationship with particle size and composition of low density lipoproteins, and their modifications by oxidation and glycation].

Low density lipoprotein (LDL) has been recognized commonly as an atherogenic lipoprotein. Especially, small dense LDL is considered to be more atherogenic than large buoyant LDL. It is contained in polydisperse LDL with various sizes and densities. Although the causative mechanism of LDL heterogeneity has not been elucidated clearly yet, it is supposed to be derived from the heterogeneous mechanism of metabolic processing of the VLDL(very low density lipoprotein)-LDL cascade different from the common pathway. It might be due to quantitative and qualitative abnormalities of secreted VLDL, different susceptibilities to lipoprotein lipase as well as hepatic lipase, and the change of receptor binding abilities of LDL. The development of polydisperse LDL has a genetic background. However, it must be influenced by some environmental factors, since the heterogeneity of LDL is restored completely to a normal monodisperse pattern concomitantly with the decreased serum triglyceride level by dietary caloric restriction. LDL is well known to be oxidized or glycated spontaneously in vivo and in vitro. Such modified LDL loses the binding affinity to the classical LDL receptor and is taken up by monocyte-derived macrophages through scavenger receptors. Since the scavenger receptor system is not down regulated, it promotes the formation of foam cells in the arterial wall accumulating cholesterol and other lipids by excess LDL uptake. Small dense LDL is considered to be easily oxidized or glycated compared with large buoyant LDL. Therefore, it might increase further the atherogenic potency by such modifications.