Several studies have suggested that the oxidative modification of
low-density lipoprotein (
LDL) could play a key role in the early stages of
atherosclerosis. The susceptibility of
LDL to oxidation has been found to be greater in patients with
coronary heart disease. Familial hypercholesterolaemia (FH) is a powerful clinical model in which to study the predictive role of
LDL in atherogenesis.
LDL-
apheresis is a treatment that is able to decrease
lipid levels in plasma. This study was aimed at investigating the reducing capacity of erythrocytes and the in vitro susceptibility to oxidation of
LDL isolated from patients with homozygous, heterozygous and double-heterozygous FH, who were treated fortnightly with
LDL-
apheresis or left untreated. In 14 FH patients, at baseline and after a cycle of treatment, the susceptibility of
LDL to oxidative modification was analysed by studying the kinetics of conjugate diene formation. Plasma hydroperoxides,
polyunsaturated fatty acid content,
LDL electrophoretic mobility on
agarose, the titre of auto-
antibodies against
oxidized LDL and serum
paraoxonase activity were also measured. Furthermore, in order to evaluate a potential relationship between
LDL oxidation and redox status, erythrocyte GSH and
ATP levels were determined in FH patients treated regularly or never treated previously by
LDL-
apheresis. Unlike in the control group, the oxidative status of
LDL in all FH patients was modified by
LDL-
apheresis, as revealed by the higher negative charge and the increase in levels of hydroperoxides and
antibodies against
oxidized LDL in the plasma. Our findings suggest both an acute effect and a long-term effect of
LDL-
apheresis in FH patients treated with
dextran sulphate
cellulose apheresis. The acute effect of
LDL-
apheresis on the susceptibility to oxidation of plasma and
LDL was demonstrated by significant decreases in plasma
hydroperoxide content, total
LDL concentration and
polyunsaturated fatty acid content. The increased resistance of
LDL to oxidation was shown by prolongation of the lag time (P<0.05) in samples after a single cycle of treatment. The long-term effect of
LDL-
apheresis was demonstrated by the comparable values for lag phases (obtained from the kinetics of conjugate diene formation) in patients under active treatment and controls. Compared with healthy controls and untreated patients, the erythrocyte GSH content was significantly higher (P</=0.001) in the treated group, suggesting the activation of reducing mechanisms.