Cholesterol-fed and casein-fed rabbit models of atherosclerosis. Part 1: Differing lesion area and volume despite equal plasma cholesterol levels.

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 (TPCCAS = 475 +/- 39 mg/dL; TPCCH = 515 +/- 70 mg/dL). The percentage of cholesterol partitioned into each of the lipoprotein fractions except high-density lipoprotein (HDL) was significantly different for the experimental groups: casein-fed rabbits had a primarily low-density lipoprotein (LDL) hypercholesterolemia while cholesterol-fed rabbits had approximately equal levels of very-low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), and LDL cholesterol. Despite matched TPC, lesions in CH animals covered twice the luminal surface area (as detected by oil red O staining; P < .05) and had three times the total volume compared with lesions in the CAS group (P < .05). Lesion volume was positively correlated with TPC and IDL and LDL cholesterol for the CAS group and with TPC and IDL cholesterol for the CH group. When the experimental groups were combined, TPC and VLDL and IDL cholesterol were positively correlated with the lesion volume. Probability of occurrence maps revealed, however, that both groups were virtually identical with respect to the topographic distribution of lesions in the thoracic and abdominal aortas. The data suggested that the differential partitioning of cholesterol into the lipoprotein fractions seen in CAS and CH rabbits influenced lesion area and volume but not topographic distribution.