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 microM while probucol had no effect at this concentration. LDL oxidized with copper in the presence of dipyridamole (20 microM) was less effective than LDL oxidized in the absence of dipyridamole at inhibiting [3H]acetyl-LDL binding to cultured human. THP-1 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.
Division of Clinical Sciences, John Curtin School of Medical Research, Australian National University, Woden Valley Hospital, Garran, ACT.
M L
ML
Selley
A L
AL
Czeti
J A
JA
McGuiness
N G
NG
Ardlie
D002478:Cells, Cultured; D004176:Dipyridamole / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000378:metabolism; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects*; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism; D011341:Probucol / Q000494:pharmacology; D017392:Thiobarbituric Acid Reactive Substances
D008077:Lipoproteins, LDL; D017392:Thiobarbituric Acid Reactive Substances; D004176:Dipyridamole; D011341:Probucol