SUSCEPTIBILITY OF LOW-DENSITY-LIPOPROTEIN TO OXIDATION IN FAMILIAL HYPERCHOLESTEROLEMIA

There is increasing evidence that oxidative modification of low densit y lipoprotein (LDL) plays an important role in the pathogenesis of ath erosclerosis. Subjects with familial hypercholesterolaemia (FH) have e levated concentrations of LDL and develop premature atherosclerosis. T he aim of the study was to determine whether the susceptibility of LDL to in vitro oxidation is increased in FH subjects. LDL was isolated f rom 15 FH homozygotes (mean age +/- SD, 19 +/- 10 years; mean LDL-chol esterol 16.86 +/- 3.55 mmol/l), 15 FH heterozygotes (38 +/- 13 years; LDL-cholesterol 5.58 +/- 1.78 mmol/l) and 15 normocholesterolaemic sub jects (31 +/- 8 years; LDL-cholesterol 3.07 +/- 0.77 mmol/l). Suscepti bility of LDL to in vitro copper-mediated oxidation was assessed by me asuring conjugated diene production at 234 nm, the lag phase being a m easure of the resistance of LDL to oxidation. Unexpectedly, the mean d uration of the lag phase was 2.2 fold longer in the FH homozygotes (12 3.8 +/- 45.0 min) and 1.75-fold longer in the FH heterozygotes(99.9 +/ - 40.6 min) than in the controls (57.1 +/- 27.9 min; P < 0.0001). Seru m and LDL vitamin E levels were higher in the FH patients, but not whe n expressed relative to LDL-cholesterol concentration. There was also no correlation between LDL vitamin E concentration and duration of the lag phase. LDL bulk rather than the susceptibility of LDL to oxidatio n is probably the more important factor for the initiation and progres sion of atherosclerosis in FH patients.