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.
Hyperlipidemia and Atherosclerosis Research Group, Clinical Research Institute of Montreal, Quebec, Canada.
L M
LM
Giroux
J
J
Davignon
M
M
Naruszewicz
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