Reduction of oxidative stress and modulation of autoantibodies against modified low-density lipoprotein after rosuvastatin therapy.
OBJECTIVE
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<or=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.


CONCLUSIONS
This study provides in vivo evidence that rosuvastatin significantly reduces oxidative stress and has immunomodulatory properties in a dose- and LDL-independent manner.
Resch
Ulrike
U
Medical University of Vienna, Wilhelm Auerswald Atherosclerosis Research Group, Vienna, Austria. ulrike.resch@meduniwien.ac.at
Tatzber
Franz
F
Budinsky
Alexandra
A
Sinzinger
Helmut
H
D000975:Antioxidants / Q000378:metabolism; D001323:Autoantibodies / Q000276:immunology*; D015415:Biomarkers / Q000097:blood; D003300:Copper / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D005464:Fluorobenzenes / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D007074:Immunoglobulin G / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008875:Middle Aged; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D009195:Peroxidase / Q000378:metabolism; D010545:Peroxides / Q000097:blood; D011743:Pyrimidines / Q000627:therapeutic use*; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000627:therapeutic use*
D000975:Antioxidants; D001323:Autoantibodies; D015415:Biomarkers; D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D008077:Lipoproteins, LDL; D010545:Peroxides; D011743:Pyrimidines; D013449:Sulfonamides; D008315:Malondialdehyde; D003300:Copper; D000068718:Rosuvastatin Calcium; D009195:Peroxidase