THE SUSCEPTIBILITY OF LOW-DENSITY-LIPOPROTEIN TO IN-VITRO OXIDATION IS INCREASED IN HYPERCHOLESTEROLEMIC PATIENTS

It has been suggested that the oxidative modification of low-density l ipoprotein (LDL) plays a major role in atherogenesis. We evaluated the oxidative resistance to copper-induced oxidative changes of LDL deriv ed from patients affected by type IIa hyperlipoproteinemia compared wi th healthy subjects and faced the question of the importance of the an tioxidants and polyunsaturated fatty acids (PUFAs) contained in LDL in determining its variability. LDL isolated from the plasmas of 25 subj ects affected by familial hypercholesterolemia and 15 control subjects was oxidatively modified with Cu2+ in vitro, and the differences in L DL susceptibilities (lag and propagation phases) to lipid peroxidation were studied by measuring the changes in fluorescence intensity. LDL alpha-tocopherol and PUFAs were also measured. The lag phase was signi ficantly lower and the propagation phase significantly higher in the t ype IIa patients than in control subjects (p < 0.01). The linoleic and arachidonic acids, expressed as percentage of total LDL fatty acids, were significantly higher in type IIa patients than in the control sub jects (p < 0.01). There was a positive significant correlation between the LDL cholesterol and the linoleic and arachidonic acids as percent age of total LDL fatty acids Cp < 0.01). Both linoleic and arachidonic acids turned out to be negatively correlated with the lag phase and p ositively with the propagation phase (p < 0.01). The concentration of LDL alpha-tocopherol was similar in the two groups. Therefore, type II a patients have a greater susceptibility to LDL oxidation than control subjects. This may be due to a relative higher concentration of linol eic and arachidonic acids in LDL derived from patients with familial h ypercholesterolemia.