The Effects of Ketoconazole on the Oxidation of Low Density Lipoproteins by Bovine Aortic Smooth Muscle Cells

Abstract

Bovine aortic smooth muscle cells (BASMC) in culture have been shown to oxidatively modify human low-density lipoprotein (LDL). Such oxidized LDL appears to be a significant factor in the etiology of atherosclerosis. This work shows that the azole antifungal drug ketoconazole when added to the culture medium of BASMC inhibits LDL oxidation. Confluent BASMC were fed 1 ml of F- 12/DMEM containing LDL (320 ug protein). The cells over a 24 hour period caused a 2x increase in LDL oxidation as measured by an increase in thiobarbituric acid reactive substances. Copper at 5 uM enhanced by 2x the oxidation of LDL by BASMC. Oxidized LDL was found to be cytotoxic to the BASMC. Addition of ketoconazole to the cell medium caused a concentration dependent inhibition of LDL oxidation by BASMC. Maximum inhibition of LDL oxidation was achieved at 20 uM of ketoconazole. BASMC viability was maintained in the presence of ketoconazole and LDL as determined by the protein content per well.