Genetics
Probucol regresses established aortic plaques in hyperlipidemic rabbits and significantly raises CETP activity, likely via antioxidant action (Atherosclerosis 1998)
Original title: Probucol treatment attenuates the aortic atherosclerosis in Watanabe heritable hyperlipidemic rabbits
This study examined whether probucol could regress aortic atherosclerosis already established in Watanabe heritable hyperlipidemic (WHHL) rabbits, treating animals for 5 months starting at 8 months of age. Aortic lesion area was significantly reduced in probucol-treated rabbits compared to untreated animals and to animals at 8 months (P less than 0.05), despite no significant difference in plasma cholesterol levels between treated and untreated groups. LDL from probucol-treated rabbits resisted copper-induced oxidation, and plasma CETP activity was significantly increased by probucol treatment (P less than 0.05). Immunohistochemistry showed macrophage-predominant lesions in untreated rabbits versus smooth-muscle-cell-predominant lesions in probucol-treated rabbits. The authors conclude probucol can regress WHHL rabbit atherosclerosis through mechanisms beyond cholesterol lowering, likely involving antioxidant activity.
Original abstract
We examined the effect of probucol on the aortic atherosclerosis already developed in Watanabe heritable hyperlipidemic (WHHL) rabbits at the initiation of treatment. In WHHL rabbits treated with probucol for 5 months from 8 months old, the lesion area in the aorta was significantly (P < 0.05) reduced when compared with that in untreated animals as well as animals at age 8 months. In contrast, plasma cholesterol levels in the probucol-treated group and untreated group during the experiment were not significantly different. LDL prepared from rabbits receiving probucol for 5 months showed resistance to oxidation by copper ions. Plasma CETP activity was significantly (P < 0.05) increased by probucol treatment. An immunohistochemical study showed that macrophages were abundant in the atherosclerotic lesions of untreated rabbits whereas smooth muscle cells were predominant in lesions of probucol-treated rabbits. These results suggest that the atherosclerotic lesion in WHHL rabbits can regress when treated by probucol and that the attenuation of atherosclerosis in this animal involves effects of probucol other than a decrease in plasma cholesterol, for example anti-oxidant activity.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.