AimsTo examine the effect of 24 weeks' rosuvastatin treatment on oxidative stress and changes in immune response to oxidized low-density lipoprotein (LDL). MethodsThis 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. ResultsDuring 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. ConclusionThis study provides in vivo evidence that rosuvastatin significantly reduces oxidative stress and has immunomodulatory properties in a dose-and LDL-independent manner.

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Amplification and over‐expression of the HER‐2/neu proto‐oncogene are associated with poor prognosis in women with both node‐positive and node‐negative breast cancer. Therefore, the encoded surface glycoprotein represents an attractive target for cancer immunotherapies. Furthermore, the extracellular domain of HER‐2/neu is released from the cell surface by proteolytic cleavage. In the present experiments, we investigated the potential biologic effects of soluble HER‐2/neu with particular emphasis on its interaction with anti‐HER‐2/neu antibodies. A monoclonal antibody specific for the extracellular domain of HER‐2/neu dose dependently inhibited the proliferation of highly HER‐2/neu‐expressing SK‐BR‐3 and BT‐474 breast cancer cells but had no effect on the proliferation of weakly to moderately HER‐2/neu‐expressing MCF‐7, HBL‐100 and ZR‐75‐1 breast cells. Addition of SK‐BR‐3 or BT‐474 cell supernatants with high concentrations of soluble HER‐2/neu led to a neutralization of anti‐HER‐2/neu antibody–mediated inhibition of proliferation due to a binding of soluble HER‐2/neu by the antibody, which could be demonstrated by immunoprecipitation. Furthermore, the ability of anti‐HER‐2/neu antibodies to mediate antibody‐dependent cellular cytotoxicity (ADCC) by lymphokine‐activated killer cells was assessed. Cytolysis of SK‐BR‐3 tumor cells was increased significantly in the presence of anti‐HER‐2/neu antibodies. Similar to the proliferation inhibition, ADCC was neutralized by addition of soluble HER‐2/neu‐containing supernatants. Our data suggest that tumors rich in HER‐2/neu might thus escape certain steps of immunologic control by neutralizing biologic activities of anti HER‐2/neu antibodies due to the presence of soluble HER‐2/neu. Int. J. Cancer 73:875–879, 1997. © 1997 Wiley‐Liss, Inc.

Elevated fibrinogen levels in high risk patients with PAD indicate an increased risk for poor outcome, particularly for fatal cardiovascular complications.