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  • Title: Probucol inhibits not only the progression of atherosclerotic disease, but causes a different composition of atherosclerotic lesions in WHHL-rabbits.
    Author: Braesen JH, Beisiegel U, Niendorf A.
    Journal: Virchows Arch; 1995; 426(2):179-88. PubMed ID: 7757289.
    Abstract:
    Watanabe heritable hyperlipidaemic (WHHL)-rabbits develop premature atherosclerosis due to an inborn defect of the low-density lipoprotein (LDL) receptor causing severe hypercholesterolaemia. Probucol, which possesses a lipid lowering and an antioxidative potency, has been shown to reduce the extent of atherosclerotic disease in this animal. The object of the present study was the detailed analysis of the cellular and non-cellular composition of atherosclerotic lesions in WHHL-rabbits treated with probucol when compared with untreated controls. In two independent sets of experiments, each consisting of one litter, a total number of 5 animals was fed a diet containing 1% (w/w) probucol. Four animals served as controls and 2 animals were sacrificed before treatment (at 2 and 4 months of age, respectively) to define the baseline level of the atherosclerotic disease. Morphometric analysis was employed in order to determine plaque area macroscopically by planimetry and plaque thickness and composition histologically, in 30 cross-sections of the aorta of each animal. In the group treated with probucol, a diminution of plaque area and thickness, as well as a decrease of foam cell and--especially in one experiment--necrotic content of atherosclerotic lesions, was observed. Plaques from aortas of animals treated with probucol consisted predominantly of smooth muscle cells and compact intercellular fibrous structures. Furthermore, as an additional characteristic feature of the "typical" probucol plaque, they usually lacked confluent necrotic cores. In comparison with untreated animals, there was also a decrease in intracellular apolipoprotein B (apo B) as determined by immunohistochemistry. These data confirm the antiatherosclerotic potency of probucol in the WHHL-rabbit. Moreover, it was demonstrated that there is a different type of atherosclerosis present in the group treated with probucol. The mechanism behind these shifts may be based on the antioxidative property as well as on direct effects of probucol on cellular plaque components.
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