Effect of probucol treatment on the susceptibility of low density lipoprotein isolated from hypercholesterolemic patients to become oxidatively modified in vitro.
Lipid accumulation in monocyte-originated macrophages in the subendothelial space is an important characteristic of atherosclerotic lesions. Several lines of evidence have indicated that this accumulation occurs as a result of lipid peroxidation. In the present study the ability of probucol to prevent oxidation of low density lipoprotein (LDL) was investigated in 20 hypercholesterolemic individuals taking part in the Probucol Quantitative Regression Swedish Trial (PQRST). The effect of Cu2(+)-induced oxidation of LDL on degradation by macrophages, binding to LDL receptors on fibroblasts and LDL TBARS content was analysed. With LDL isolated from patients on diet alone oxidation led to a 44.3% decreased binding to fibroblasts (P less than 0.001), a ninefold increased uptake in macrophages (P less than 0.001) and a twentyfold increase in TBARS content (P less than 0.001) as compared to native LDL. These values were essentially the same during treatment with cholestyramine alone. However, during treatment with probucol plus cholestyramine exposure of LDL to Cu2+ resulted in an increase in TBARS which was less than 50% (P less than 0.02) of that observed during the other two treatment periods. Furthermore, probucol treatment abolished more than 70% of the decrease in B,E receptor binding to fibroblasts (P less than 0.05) and more than 90% of the increased degradation by macrophages (P less than 0.001) of Cu2+ oxidatively modified LDL.
Regnström
J
J
King Gustaf V Research Institute, Karolinska Hospital, Stockholm, Sweden.
Walldius
G
G
Carlson
L A
LA
Nilsson
J
J
D000368:Aged; D002478:Cells, Cultured; D002784:Cholesterol / Q000097:blood; D002792:Cholestyramine Resin / Q000627:therapeutic use; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D005526:Food, Formulated; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy*; D008077:Lipoproteins, LDL / Q000097:blood*; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction / Q000187:drug effects; D010636:Phenols / Q000494:pharmacology*; D011341:Probucol / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D011973:Receptors, LDL / Q000378:metabolism
D005227:Fatty Acids; D008077:Lipoproteins, LDL; D010636:Phenols; D011973:Receptors, LDL; D002792:Cholestyramine Resin; D002784:Cholesterol; D011341:Probucol