Factors affecting resistance of low density lipoproteins to oxidation

Oxidation resistance (OR) of low density lipoproteins (LDL) is frequently determined by the conjugated diene (CD) assay, in which isolated LDL is exposed to Cu2+ as prooxidant in the range of 1-10 mu M. A brief review on major findings obtained with this assay will be given. A consistent observation is that vitamin E supplements or oleic acid-rich diets increase OR. Oxidation indices measured by the CD assay and effects of antioxidants very significantly depend on the Cu2+ concentration used for LDL oxidation. For medium and high Cu2+ concentrations, the relationship between lag time and propagation rate can be described by a simple hyperbolic saturation function, which has the same mathematical form as the Michaelis-Menten equation. At medium and high Cu2+ concentrations (0.5 to 5 mu M), vitamin E increases lag time in a dose-dependent manner. The increase is higher for 0.5 mu M Cu2+ as compared to 5 mu M. At low Cu2+ concentrations (0.5 mu M or less), the mechanism of LDL oxidation changes. Significant oxidation occurs in a preoxidation phase, which commences shortly after addition of Cu2+ Preoxidation is not inhibited by vitamin E. It is concluded that much additional work is needed to validate the importance of oxidation indices derived from CD and similar assays.