Sequential change in physicochemical properties of LDL during oxidative modification

Oxidized LDL is thought to be a highly atherogenic lipoprotein. Structural background of this pathogenesis, however, has not yet been well defined. Physicochemical characterization of this lipoprotein is still controversial, which therefore makes it difficult to take a mechanistic approach to its atherogenicity. We thus conducted investigation of time-dependent changes in chemical compositions and alternation of physical properties of LDL in detail during its oxidation induced by human embryonic endothelial cells and copper ions. The oxidation caused hydrolysis of glycerolipids being demonstrated as decrease of triglyceride and choline-phospholipid and increase of lysophosphatidylcholine. Fragmentation of apoB was also induced while over-all protein components stayed with the particles. The density of the particles continuously shifted to higher fractions for all the particles to reach d ≥ 1.044 after 10 h incubation. The average diameter of LDL, however, decreased from 28.1 nm to 25.6 nm by 5 h and increased to 27.1 nm towards 20 h incubation with the increase of discoid particles. These dynamic changes can be interpreted by losing fatty acyl group from the core lipid components perhaps due to oxidative degradation and by increase of surface lysophosphatidylcholine to cause remodeling of the particles.