Induction of Atherosclerosis by Low-Fat, Semisynthetic Diets in LDL Receptor–Deficient C57BL/6J and FVB/NJ Mice: Comparison of Lesions of the Aortic Root, Brachiocephalic Artery, and Whole Aorta (En Face Measurement)

OBJECTIVE—A semisynthetic diet with varying amounts of cholesterol was used to achieve hypercholesterolemia and atherosclerosis in LDL receptor–deficient (LDLR−/−) mice. Atherosclerotic lesions were measured as cross-sectional area at the aortic root and brachiocephalic artery and by en face analysis of aortic lesion area in 209 male and female animals on the C57BL/6J (B6.LDLR−/−) and FVB/NJ (FVB.LDLR−/−) backgrounds. METHODS AND RESULTS—The semisynthetic diet containing 4.3% fat and 0.00% or 0.02% cholesterol was sufficient to induce hypercholesterolemia (12.6±2.4 mmol/L) and atherosclerosis in B6.LDLR−/− mice at the aortic root (98 980±37 727 μm) and brachiocephalic artery (12 039±12 750 μm) but did not produce significant lesions in the aorta measurable by the en face method. Raising dietary cholesterol to 0.15%, 0.30%, or 0.50% more than doubled plasma cholesterol levels (35.9±8.5 mmol/L) and resulted in significant en face lesions. It also led to a significant increase in atherosclerotic lesion area at the aortic root (547 753±182 151 μm) and brachiocephalic arteries (125 666±59 339 μm). Although FVB.LDLR−/− mice developed comparable cholesterol levels, they were relatively atherosclerosis resistant and had many-fold smaller lesions. CONCLUSIONS—These results should aid investigations of atherosclerosis in LDLR−/− mice by informing the selection of diet to be used and the location of lesions to be scored.