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 mum(2)) and brachiocephalic artery (12 039 +/- 12 750 mum(2)) 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 mum(2)) and brachiocephalic arteries (125 666 +/- 59 339 mum(2)). 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.