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Abstract
A biochemical, histologic and morphometric evaluation of spontaneous, diet-induced
(thoracic aorta) and injury-induced (iliac-femoral) atherosclerotic lesions was performed
in rabbits maintained on varying levels of dietary cholesterol. Rabbits were meal-fed
a 3% peanut oil, 3% coconut oil diet containing 0%, 0.1%, 0.25/x, 0.5%, 1.0%, 1.5%
or 2.0% cholesterol for 9 weeks. Plasma total cholesterol exposure (area under cholesterol-time
curve (TC-AUC)) increased diet-dependently over the course of the study. VLDL and
LDL cholesterol (VLDL-C, LDL-C) comprised 41% and 55%, respectively, of the plasma
total cholesterol at cholesterol levels > 700 mg/dl (TC-AUC > 31 868 mg day/dl) and
both VLDL-C and LDL-C were linearly related to TC-AUC (r = 0.98). Plasma TC-AUC was linearly related to thoracic aortic cholesteryl ester
(CE) content (r = 0.74) and thoracic aortic lesion coverage (r = 0.66). In the injury-induced iliac-femoral lesion, plasma TC-AUC was linearly related
to both iliac-femoral CE content (r = 0.80) and macrophage/lesion ratio (r = 0.64). At plasma cholesterol levels greater than 700 mg/dl, CE content of the iliac-femoral
lesion ranged from 35 to 69 μg/mg dry defatted tissue, > 75% of the lesions were fibrofoamy
in nature and macrophage/lesion area ratio was 0.46 to 0.55 while lesion area remained
constant. VLDL-C and LDL-C were highly correlated with the CE content of both thoracic
and iliac-femoral lesions, thoracic aortic lesion coverage and macrophage/lesion area
ratio (r = 0.86–0.99). We conclude that the composition, extent and type of atherosclerotic
lesion induced in rabbits is dependent upon the overall plasma cholesterol exposure,
VLDL and LDL cholesterol content and whether lesions are induced by diet alone or
both diet and chronic endothelial injury. In addition, various stages of atherosclerotic
lesion formation can be replicated in the rabbit by titrating the animal's overall
plasma cholesterol exposure.
Keywords
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Article info
Publication history
Accepted:
March 26,
1993
Received in revised form:
March 26,
1993
Received:
February 1,
1993
Identification
Copyright
© 1993 Published by Elsevier Inc.
