Atherosclerosis mouse model induced by a high-cholesterol diet supplemented with beta-aminopropionitrile: effects of various anti-atherosclerotic agents on the biochemical parameters.
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.
Yamaguchi
Y
Y
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Mukogawa Women's, Nishinomiya, Japan.
Yamada
K
K
Kitagawa
S
S
Kunitomo
M
M
D010129:4-Aminobenzoic Acid / Q000627:therapeutic use; D000629:Aminopropionitrile / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000737:chemistry / Q000187:drug effects; D001161:Arteriosclerosis / Q000097:blood / Q000209:etiology*; D001835:Body Weight; D002784:Cholesterol / Q000032:analysis*; D002791:Cholesterol, Dietary / Q000009:adverse effects*; D002994:Clofibrate / Q000627:therapeutic use; D004195:Disease Models, Animal; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D051379:Mice; D010196:Pancreatic Elastase / Q000627:therapeutic use*; D062366:para-Aminobenzoates
D002791:Cholesterol, Dietary; D000960:Hypolipidemic Agents; D062366:para-Aminobenzoates; D000629:Aminopropionitrile; D002784:Cholesterol; C018246:cetaben; D010196:Pancreatic Elastase; D002994:Clofibrate; D010129:4-Aminobenzoic Acid