Acute and long-term effects of low-density lipoprotein (LDL)-apheresis on oxidative damage to LDL and reducing capacity of erythrocytes in patients with severe familial hypercholesterolaemia

Several studies have suggested that the oxidative modification of low-densi ty lipoprotein (LDL) could play a key role in the early stages of atheroscl erosis. The susceptibility of LDL to oxidation has been found to be greater in patients with coronary heart disease. Familial hypercholesterolaemia (F H) is a powerful clinical model in which to study the predictive role of LD L in atherogenesis. LDL-apheresis is a treatment that is able to decrease l ipid levels in plasma. This study was aimed at investigating the reducing c apacity of erythrocytes and the in vitro susceptibility to oxidation of LDL isolated from patients with homozygous, heterozygous and double-heterozygo us FH, who were created fortnightly with LDL-apheresis or left untreated. I n 14 FH patients, at baseline and after a cycle of treatment, the susceptib ility of LDL to oxidative modification was analysed by studying the kinetic s of conjugate diene formation. Plasma hydroperoxides, polyunsaturated fatt y acid content, LDL electrophoretic mobility on agarose, the titre of auto- antibodies against oxidized LDL and serum paraoxonase activity were also me asured. Furthermore, in order to evaluate a potential relationship between LDL oxidation and redox status, erythrocyte GSH and ATP levels were determi ned in FH patients treated regularly or never treated previously by LDL-aph eresis. Unlike in the control group, the oxidative status of LDF 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 sulp hate cellulose apheresis. The acute effect of LDL-apheresis on the suscepti bility to oxidation of plasma and LDL was demonstrated by significant decre ases in plasma hydroperoxide content, total LDL concentration and polyunsat urated 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 con jugate diene formation) in patients under active treatment and controls. Co mpared with healthy controls and untreated patients, the erythrocyte GSH co ntent was significantly higher (P<less than or equal to> 0.001) in the trea ted group, suggesting the activation of reducing mechanisms.