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Decreased susceptibility of low-density lipoproteins to in-vitro oxidation after dextran-sulfate LDL-apheresis treatment

  • Norbert Leitinger
    Affiliations
    Department of Cardiology, Center for Health Sciences, UCLA Medical School, Los Angeles, CA, USA
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  • Christian Pirich
    Correspondence
    Corresponding author, Department of Nuclear Medicine, University of Vienna, Währinger Gürtel 18–20, 1090 Vienna, Austria. Tel.: + 43 1 404005534; fax: + 43 1 404005532.
    Affiliations
    Department of Nuclear Medicine, University of Vienna and Institute for Diagnosis and Treatment of Lipid Disorders (ATHOS), Nadlergasse 1, A-1090 Vienna, Austria
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  • Ingrid Blazek
    Affiliations
    Department of Nuclear Medicine, University of Vienna and Institute for Diagnosis and Treatment of Lipid Disorders (ATHOS), Nadlergasse 1, A-1090 Vienna, Austria
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  • Georg Endler
    Affiliations
    Department of Nuclear Medicine, University of Vienna and Institute for Diagnosis and Treatment of Lipid Disorders (ATHOS), Nadlergasse 1, A-1090 Vienna, Austria
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  • Helmut Sinzinger
    Affiliations
    Department of Nuclear Medicine, University of Vienna and Institute for Diagnosis and Treatment of Lipid Disorders (ATHOS), Nadlergasse 1, A-1090 Vienna, Austria
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      Abstract

      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-F (8-iso-PGF), 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.

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