© 1995 American Heart Association, Inc.
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Reduction of Serum Cholesterol Levels Alters Lesional Composition of Atherosclerotic Plaques
Effect of Pravastatin Sodium on Atherosclerosis in Mature WHHL Rabbits
From the Institute for Experimental Animals, Kobe University School of Medicine (M.S., T.I., T.Y., Y.W.); the Second Department of Internal Medicine, Sanraku Hospital (T.T.); and the Pharmacology and Molecular Biology Research Laboratories (Y.T.), Biological Research Laboratories (M.F., J.F., T.H.), and the New Drug Development Department (A.T.), Sankyo Co, Ltd, Tokyo, Japan.
Correspondence to Masashi Shiomi, PhD, Institute for Experimental Animals, Kobe University School of Medicine, Kusunoki-cho, Chuo-ku, Kobe 650, Japan.
Abstract We examined whether serum cholesterol reduction alters the lesional composition of atherosclerotic plaques. To reduce serum cholesterol levels, we gave pravastatin sodium, a 3-hydroxy-3-methylglutaryl Coenzyme A reductase inhibitor, to mature Watanabe heritable hyperlipidemic rabbits, an LDL receptor–deficient animal model, for 48 weeks. Atherosclerotic lesions were immunohistochemically and conventionally stained and each lesional component area was measured by a color image analyzer. Compared with those of a placebo group, serum LDL cholesterol levels were reduced by 22% (P<.05). Data for atherosclerosis indicated a significant decrease in percent of surface lesion area (26% reduction) and in intimal thickening (30% reduction) in the abdominal aorta, as well as in coronary stenosis (29% reduction). Data for lesional composition indicated a significant decrease in the percent area of macrophage plus extracellular lipid deposits in aortic lesions (32% reduction) and coronary lesions (45% reduction). A significant increase was observed in the percent area of collagen in aortic lesions and in the percent area of smooth muscle cells in coronary lesions. The plaques seemed to become stable lesions as a result of pravastatin treatment. In conclusion, a long-term reduction of serum LDL cholesterol reduced lipid-related lesional components, in addition to suppressing the progression of established atherosclerosis.
Key Words: cholesterol reduction • macrophages • smooth muscle cells • atherosclerosis • WHHL rabbit
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