One-month-old male New Zealand White rabbits were fed either a cholesterol-free casein diet (CAS; n=10); low-level cholesterol-supplemented (0.125% to 0.5% by weight) chow (CH; n=10); or standard laboratory rabbit chow (n=3) for 24 weeks, during which total plasma cholesterol (TPC) levels were matched for the two experimental groups (TPC CAS =475±39 mg/dL; TPCCH=515±70 mg/dL 2 demonstrated that the atherogenic component of the diet was cholesterol. Their pioneering experiment, in which dietary cholesterol was used to induce hyperlipidemia that resulted in atherosclerotic lesions, established the rabbit as an experimental model of atherosclerosis that is still used today. More recently, it has been discovered 3 that a cholesterol-free, casein-enriched diet induces an endogenous hypercholesterolemia that also results in atherosclerotic lesion formation.Induction of hypercholesterolemia in the rabbit with dietary cholesterol results in a very-low-density lipoprotein (VLDL) hypercholesterolemia in which the VLDL particles, enriched in cholesterol, 4 migrate as ^-lipoproteins on agarose gel electrophoresis and are thus often referred to as /J-VLDL.
"7 In contrast, induction of hypercholesterolemia in the rabbit by using a semipurified diet enriched in casein results in a low-density lipoprotein (LDL) hypercholesterolemia similar to that seen in humans. 8 For this reason, the casein-fed rabbit has been used extensively in biochemical studies of lipoprotein metabolism. Only a few groups have characterized different rabbit models of atherosclerosis by using both extensive biochemical analyses and detailed morphological examinations of lesion formation.1417 However, extensive morphological evaluation including lesion area, volume, and topographic distribution has not been performed. In 1978, Ross et al 18 examined the characteristics of the casein-fed and the cholesterol-fed rabbit models to compare the effects of different lipoprotein profiles on atherosclerotic lesion formation. When animals were matched for total plasma cholesterol (TPC), the caseinfed and cholesterol-fed rabbits, although differing in lipoprotein profile, had the same extent of lesion formation. In an attempt to fully characterize the caseinfed and the cholesterol-fed rabbit models of atherosclerosis, in the present study we examined the lipoprotein profiles and the atherosclerotic lesions in the entire aorta of rabbits fed a semisynthetic diet enriched in casein and in rabbits fed a cholesterol-supplemented diet. Because the two groups were matched for TPC, we were able to examine the effect of the different lipoprotein profiles in these animals on the extent, volume, and topographic distribution of lesion formation. The relation of the lipoprotein profiles of these animals to the microscopic morphology and site specificity of lesion type is presented in the accompanying article.