Reduction of oxidative stress and modulation of autoantibodies against modified low‐density lipoprotein after rosuvastatin therapy

• Published in: British journal of clinical pharmacology 2006-03, Vol.61 (3), p.262-274
• Main Authors: Resch, Ulrike, Tatzber, Franz, Budinsky, Alexandra, Sinzinger, Helmut
• Format: Article
• Language: English
• Subjects: Antioxidants - metabolism; autoantibodies; Autoantibodies - immunology; Biological and medical sciences; Biomarkers - blood; Copper - metabolism; Dose-Response Relationship, Drug; Female; Fluorobenzenes - therapeutic use; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use; Immunoglobulin G - immunology; Immunoglobulin M - immunology; Lipoproteins, LDL - metabolism; Male; Malondialdehyde - metabolism; Medical sciences; Middle Aged; Oxidation-Reduction; oxidative stress; Oxidative Stress - drug effects; oxidatively modified low‐density lipoprotein; Peroxidase - metabolism; Peroxides - blood; Pharmacodynamics; Pharmacology. Drug treatments; Pyrimidines - therapeutic use; rosuvastatin; Rosuvastatin Calcium; Sulfonamides - therapeutic use
• ISSN: 0306-5251; 1365-2125
• DOI: 10.1111/j.1365-2125.2005.02568.x

Aims To examine the effect of 24 weeks’ rosuvastatin treatment on oxidative stress and changes in immune response to oxidized low‐density lipoprotein (LDL). Methods This was an open‐label study of patients in Austria receiving 10 or 40 mg rosuvastatin daily alternately during 12 and 24 weeks. Circulating concentrations of antibodies to malondialdehyde‐oxidized LDL (MDA‐LDL), both IgG and IgM type, to copper‐oxidized LDL (Cu‐OxLDL‐IgG), concentrations of oxidized LDL complexed to IgG (OxLDL‐IC) and markers of oxidative stress and systemic inflammation in subjects with plasma LDL cholesterol concentrations between 130 mg dl−1 and 250 mg dl−1 and triglycerides ≤ 400 mg dl−1 were determined. Results During statin therapy, plasma endogenous peroxides (POX‐ACT) concentrations and peroxidase activity were significantly decreased, associated with a modest increase in total antioxidant capacity (TAC). Antibody titres to MDA‐LDL‐IgM, Cu‐OxLDL‐IgG and OxLDL‐IC decreased, whereas MDA‐LDL‐IgG concentrations were increased after therapy. These changes were dose‐ and LDL‐independent. POX‐ACT concentrations were significantly positively correlated with inflammation markers before and after therapy and inversely with high‐density lipoprotein‐cholesterol concentrations after therapy. Conclusion This study provides in vivo evidence that rosuvastatin significantly reduces oxidative stress and has immunomodulatory properties in a dose‐ and LDL‐independent manner.