Decreased susceptibility of low-density lipoproteins to in-vitro oxidation after dextran-sulfate LDL-apheresis treatment.
Low-density lipoproteins (LDL)-apheresis is a well established treatment of severe hypercholesterolemia resulting in fast clinical improvement and angiographically proven regression after 6 months of therapy. The underlying mechanisms, beside lipoprotein removal, are still under debate. Recently, oxidized LDL were shown to be of key importance in foam cell formation and atherosclerotic lesion development. We examined the influence of dextran-sulfate LDL-apheresis on the susceptibility of LDL to oxidation in 6 patients (5 males, 1 female, age: 41-60 years) suffering from severe heterozygous hypercholesterolemia or combined hyperlipidemia. LDL-apheresis influenced the oxidizability of LDL by a significant (P < 0.01) prolongation of the median of lag time (min) for LDL samples (before treatment 75, range: 31-176 versus after treatment 129.5, range 45-286). A significant (P < 0.01) difference could be also observed in the amount of conjugated dienes as expressed by the maximum rate in absorbance (before treatment 15.39, range: 5.29-21.22 versus after treatment 20.20, range 12.88-72.33). Thiobarbituric acid reactive substances (TBARS) formation was significantly decreased in LDL obtained after apheresis treatment as compared to pretreatment LDL. Electrophoretic mobility (EM) of LDL obtained before and after LDL-apheresis revealed a significant increase (P < 0.05) from a mean of 8.8 +/- 0.5 to a mean of 10.5 +/- 0.5 mm. The titers of plasma autoantibodies against oxLDL (oLAb) which varied considerably interindividually, were not influenced by LDL-apheresis treatment. Levels of F2-isoprostanes, as measured by plasma levels of 8-iso-prostaglandin-F2 alpha (8-iso-PGF2 alpha), reflecting oxidative stress, did not change, either. In summary, our findings provide evidence that even one single dextran sulfate LDL-apheresis treatment decreases LDL-oxidizability, which is an additional beneficial effect to that of lipid lowering.
Department of Cardiology, Center for Health Sciences, UCLA Medical School, USA.
N
N
Leitinger
C
C
Pirich
I
I
Blazek
G
G
Endler
H
H
Sinzinger
D000328:Adult; D001323:Autoantibodies / Q000032:analysis; D001781:Blood Component Removal; D016264:Dextran Sulfate; D015237:Dinoprost / Q000031:analogs & derivatives / Q000097:blood; D004587:Electrophoresis, Agar Gel; D028441:F2-Isoprostanes; D005260:Female; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D006950:Hyperlipidemia, Familial Combined / Q000097:blood / Q000628:therapy*; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000628:therapy*; D066298:In Vitro Techniques; D008077:Lipoproteins, LDL / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D001323:Autoantibodies; D028441:F2-Isoprostanes; D008077:Lipoproteins, LDL; D017392:Thiobarbituric Acid Reactive Substances; C075750:8-epi-prostaglandin F2alpha; D006493:Heparin; D016264:Dextran Sulfate; D015237:Dinoprost