A mouse model of
atherosclerosis was produced by feeding a 1.5%
cholesterol diet with 0.4%
beta-aminopropionitrile (
BAPN) fumarate, a chemical lathyrogen, for 10 weeks, and the pharmacological sensitivity and specificity of this model were evaluated biochemically with various
hypolipidemic drugs and
calcium antagonists. Histological findings on this model showed typical angiolathyrism with foam cells in the media of the thoracic aorta. Uniform and marked accumulation of
cholesterol, notably esterified
cholesterol, in the aorta was observed, although it was much less in mice receiving a high-
cholesterol diet or
BAPN alone. The reduction in
elastin contents in the aorta was a characteristic feature of this model.
Clofibrate,
cetaben and
elastase tended to prevent the increase of
cholesterol contents in the aorta, together with their significant hypocholesterolemic effects.
Nifedipine,
diltiazem and
verapamil showed a slight preventive effect on the
cholesterol accumulation and on the reduction of
elastin content in the aorta without a
cholesterol lowering effect in the serum.
MgCl2 was more effective than other
calcium antagonists and even had a hypocholesterolemic effect. The results indicate that this mouse
atherosclerosis model may be usable for primary
drug evaluation.