title: 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.
abstract: 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.
authors.affiliation: Plasmapheresis Unit, Istituto di Terapia Medica Sistematica, University of Rome La Sapienza, Azienda Policlinico Umberto I, Viale del Policlinico, 00161 Rome, Italy. c.incas@mail.flashnet.it
authors.forename: C
authors.initials: C
authors.lastname: Stefanutti
authors.forename: S
authors.initials: S
authors.lastname: Di Giacomo
authors.forename: A
authors.initials: A
authors.lastname: Vivenzio
authors.forename: G C
authors.initials: GC
authors.lastname: Isacchi
authors.forename: R
authors.initials: R
authors.lastname: Masella
authors.forename: P
authors.initials: P
authors.lastname: Caprari
authors.forename: R
authors.initials: R
authors.lastname: Varì
authors.forename: A
authors.initials: A
authors.lastname: Tarzia
authors.forename: A
authors.initials: A
authors.lastname: Mosiello
authors.forename: A
authors.initials: A
authors.lastname: Cantafora
mesh_terms: D000255:Adenosine Triphosphate / Q000097:blood; D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D004587:Electrophoresis, Agar Gel; D004912:Erythrocytes / Q000378:metabolism / Q000502:physiology*; D005231:Fatty Acids, Unsaturated / Q000097:blood; D005260:Female; D005978:Glutathione / Q000097:blood; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000628:therapy*; D008054:Lipid Peroxides / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood* / Q000502:physiology; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D010956:Plasmapheresis
chemical_list: D005231:Fatty Acids, Unsaturated; D008054:Lipid Peroxides; D008077:Lipoproteins, LDL; D000255:Adenosine Triphosphate; D005978:Glutathione