Simvastatin inhibits the oxidation of low-density lipoproteins by activated human monocyte-derived macrophages.
Human monocyte-derived macrophages treated with increasing concentrations of the HMG-CoA reductase inhibitor, simvastatin, showed a dose-dependent decrease in superoxide formation in response to activation by phorbol myristate acetate. As a consequence, they oxidized LDL much less than untreated cells. Addition of exogenous mevalonic acid to simvastatin-treated macrophages restored their ability for superoxide production and for oxidative modification of LDL. These results indicate that simvastatin might prevent atherosclerosis by additional mechanisms besides its hypocholesterolemic activity.
Giroux
L M
LM
Hyperlipidemia and Atherosclerosis Research Group, Clinical Research Institute of Montreal, Quebec, Canada.
Davignon
J
J
Naruszewicz
M
M
D004347:Drug Interactions; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000494:pharmacology*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008148:Lovastatin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D008262:Macrophage Activation; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D008798:Mevalonic Acid / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects; D010084:Oxidation-Reduction / Q000187:drug effects; D019821:Simvastatin; D013481:Superoxides / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008077:Lipoproteins, LDL; D013481:Superoxides; D008148:Lovastatin; D019821:Simvastatin; D006903:Hydroxymethylglutaryl CoA Reductases; D013755:Tetradecanoylphorbol Acetate; D008798:Mevalonic Acid