Effect of simvastatin on the oxidation of native and modified lipoproteins

Modified (oxidized) low-density lipoprotein (LDL) plays a significant role in atherosclerosis by accumulation in arteries. Also, glycated LDL, such as in diabetics, are increasing the risk for atherosclerosis, due to an increased oxidizability as compared to native LDL. For these reasons, the potential inhibition of such modifications is of clinical importance. We investigated the influence of simvastatin on oxidation of native and modified LDL as well as high-density lipoprotein (HDL), which plays a protective role in atherosclerosis. Quantitative assessment of the oxidation end-product malondialdehyde (MDA) revealed the highest inhibitory rate for HDL at concentrations of 1.6 microg/ml and 0.8 microg/ml by 30.3% and 20.4%, at 6 h and 4 h, respectively. At 24 h, the inhibition was still persisting amounting to 27.9% and 20.3%, respectively. For native LDL, we found less inhibition of oxidation at a concentration of 1.6 microg/ml amounting to 19.2% and 11.5%, for 4 h and 6 h, respectively. Similar effects were found at a concentration of 0.8 microg/ml. For modified, glycated LDL, the most pronounced effect was found at a concentration of 1.6 microg/ml amounting to 22.4% for the period of 2-24 h of oxidation. For glycoxidated LDL, the inhibition of oxidation was less expressed amounting to 10.1% for the period of 2-6 h at the same concentration. The influence of simvastatin on lag time (protection from oxidation) by diene conjugation was also investigated. At the highest concentration of simvastatin (1.6 microg/ml), we found a prolongation of lag time from 73 min to 99 min for native LDL, for glycoxidated LDL 60 min to 89 min and for HDL 54 min to 64 min. For glycated LDL, only a small decrease of lag time (66 min versus 71 min) at same concentration was observed. For glycated and glycoxidated LDL, we found a moderate increase in relative electrophoretic mobility (REM) by 2.0 and 2.3, respectively, but no changes in the presence of simvastatin were observed. These data show that simvastatin besides its lipid-lowering action has also significant antioxidative properties.