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Probucol Prevents the Progression of Atherosclerosis in Watanabe Heritable Hyperlipidemic Rabbit, an Animal Model for Familial Hypercholesterolemia
Toru Kita, Yutaka Nagano, Masayuki Yokode, Kenji Ishii, Noriaki Kume, Akira Ooshima, Haruyoshi Yoshida and Chuichi Kawai
Proceedings of the National Academy of Sciences of the United States of America
Vol. 84, No. 16 (Aug. 15, 1987), pp. 5928-5931
Published by: National Academy of Sciences
Stable URL: http://www.jstor.org/stable/30153
Page Count: 4
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In this study, we questioned whether in vivo probucol could prevent the progression of atherosclerosis in homozygous Watanabe heritable hyperlipidemic (WHHL) rabbits, an animal model for familial hypercholesterolemia. At 2 months of age, eight WHHL rabbits were divided into two groups. Group A (n = 4) was fed standard rabbit chow for 6 months. Group B (n = 4) was fed standard rabbit chow containing 1% probucol for 6 months. At the end of the experiments, average plasma concentrations of cholesterol were 704 ± 121 mg/dl in group A and 584 ± 61 mg/dl in group B, respectively. The percentage of surface area of total thoracic aorta with visible plaques in group A versus group B was 54.2% ± 18.8% versus 7.0% ± 6.3%, respectively. What was noteworthy was that the percentage of plaque in the descending thoracic aorta was almost negligible (0.2% ± 0.2%) in group B rabbits compared to that in group A rabbits (41.1% ± 20.2%). Low density lipoproteins (LDL) isolated from WHHL rabbits under treatment with probucol (group B) were shown to be highly resistant to oxidative modification by cupric ion and to be minimally recognized by macrophages. On the contrary, LDL from group A rabbits incubated with cupric ion showed a 7.4-fold increase in peroxides (thiobarbituric acid-reactive substances) and a 4.3-fold increase in the synthesis of cholesteryl ester in macrophages compared to those of LDL from group B rabbits. Thus, probucol could definitely prevent the progression of atherosclerosis in homozygous WHHL rabbits in vivo by limiting oxidative LDL modification and foam cell transformation of macrophages.
Proceedings of the National Academy of Sciences of the United States of America © 1987 National Academy of Sciences