Rabbits

The rabbit has the distinction of being the first species recognized to develop diet-induced atheromatous lesions, in the landmark report by Anitschkow in 1914 (Anitschkow, 1914). New Zealand white rabbits develop lesions primarily in the aorta, and their development is associated with extraordinarily high plasma cholesterol levels (in the 1000-3000 mg/dl range), which can compromise other organ systems in ways that affect the experimental utility of this model. Disease of epicardial coronary vessels is rarely described, and though some features of human atheroma are present in the aortic lesions in rabbits, the prominent human concern of plaque instability is not a feature.

The use of rabbits as models of atherosclerosis has been enhanced significantly by development of genetic models, including the Watanabe heritable hyperlipidemic rabbit, which carries a spontaneous mutation in the LDL receptor (Watanabe, 1980). These rabbits develop aortic lesions spontaneously, and thus they serve as a particularly useful model to test mechanical and pharmacological interventions in atherosclerosis-related conditions. However, even in these genetically defined rabbits, intervals of at least a year are required for the development and progression of advanced lesions, and therefore time and cost issues factor into the choice of this model.

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