Plaque Rupture After Short Periods of Fat Feeding in the Apolipoprotein E–Knockout Mouse

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Abstract
Background— These studies examined the early time course of plaque development and destabilization in the brachiocephalic artery of the apolipoprotein E–knockout mouse, the effects of pravastatin thereon, and the effects of pravastatin on established unstable plaques. Methods and Results— Male apolipoprotein E–knockout mice were fed a high-fat, cholesterol-enriched diet from the age of 8 weeks. Animals were euthanized at 1-week intervals between 4 and 9 weeks of fat feeding. Acutely ruptured plaques were observed in the brachiocephalic arteries of 3% of animals up to and including 7 weeks of fat feeding but in 62% of animals after 8 weeks, which suggests that there is a sharp increase in the number of plaque ruptures at 8 weeks. These acute plaque ruptures then appear to heal and form buried fibrous caps; after 9 weeks of fat feeding, mice had 1.05±0.15 buried fibrous caps at a single site in the brachiocephalic artery. Pravastatin (40 mg/kg of body weight per day for 9 weeks; resultant plasma concentrati...