Effects of probucol on atherosclerosis of apoE-deficient or LDL receptor-deficient mice.
The effect of probucol on atheroma formation was evaluated using mouse models for atherosclerosis with different diet protocols. Dietary administration of probucol (0.5 %, wt/wt) for 12 weeks reduced total plasma cholesterol levels in both apolipoprotein E (apoE)-deficient mice fed a western diet and in low-density lipoprotein receptor (LDLR)-deficient mice fed a Paigen diet by 60 % and 30 % to 60 %, respectively. Probucol treatment also significantly reduced high-density lipoprotein (HDL) levels in apoE-deficient mice, but not in LDLR-deficient mice. Atherosclerotic plaques in the aortic sinus of probucol-treated apoE-deficient mice were two-fold larger than those in untreated apoE-deficient mice, while the lesions in probucol-treated LDLR-deficient mice were similar to those in untreated LDLR-deficient mice. A strong negative correlation between HDL cholesterol levels and lesion sizes at the aortic sinus was observed in apoE-deficient mice, but not in LDLR-deficient mice. Thus, in contrast to LDLR-deficient mice, probucol had a strong proatherogenic effect in the aortic sinus of apoE-deficient mice associated with the reduction of HDL levels in spite of the reduction of total plasma cholesterol levels. The varying effects of probucol on atherogenesis depend upon the portion of aorta and which animal model is evaluated, implicating that complex cellular events are involved in the effect of probucol.
Yoshikawa
T
T
Department of Metabolic Diseases, Faculty of Medicine, University of Tokyo, Tokyo, Japan.
Shimano
H
H
Chen
Z
Z
Ishibashi
S
S
Yamada
N
N
D000818:Animals; D000924:Anticholesteremic Agents / Q000378:metabolism; D001057:Apolipoproteins E / Q000172:deficiency* / Q000378:metabolism; D001161:Arteriosclerosis / Q000378:metabolism* / Q000473:pathology; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D008055:Lipids / Q000097:blood; D008075:Lipoproteins, HDL / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D011341:Probucol / Q000097:blood / Q000494:pharmacology*; D011973:Receptors, LDL / Q000172:deficiency* / Q000378:metabolism; D012850:Sinus of Valsalva / Q000473:pathology
D000924:Anticholesteremic Agents; D001057:Apolipoproteins E; D008076:Cholesterol, HDL; D008055:Lipids; D008075:Lipoproteins, HDL; D011973:Receptors, LDL; D002784:Cholesterol; D011341:Probucol