DIPYRIDAMOLE INHIBITS THE OXIDATIVE MODIFICATION OF LOW-DENSITY-LIPOPROTEIN

The oxidative modification of low density lipoprotein (LDL) is believed to play an important role in the initiation of the atherosclerotic lesion. Dipyridamole, which is used clinically as a coronary vasodilator and an antiplatelet agent, has antioxidant properties. Probucol is a lipid-lowering agent which inhibits the oxidative modification of LDL. We have compared the effect of pharmacological concentrations of dipyridamole and probucol on the oxidative modification of LDL by copper or endothelial cells in vitro. Dipyridamole protected LDL from oxidative modification by either copper ions or endothelial cells at concentrations as low as 2.5 mu M while probucol had no effect at this concentration. LDL oxidized with copper in the presence of dipyridamole (20 mu M) was less effective than LDL oxidized in the absence of dipyridamole at inhibiting [H-3]acetyl-LDL binding to cultured human THP-I monocyte derived macrophages. The concentrations of dipyridamole found to inhibit the oxidative modification of LDL in vitro are achieved in vivo using clinically recommended doses.