on August 7, 2003
Arteriosclerosis, Thrombosis, and Vascular Biology. 2003
Published online before print August 7, 2003, doi: 10.1161/01.ATV.0000090126.34881.B1
Published online before print August 7, 2003, doi: 10.1161/01.ATV.0000090126.34881.B1
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Submitted on May 29, 2003
Accepted on July 28, 2003
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)
Daniel Teupser ;
From the Laboratory of Biochemical Genetics and Metabolism, The Rockefeller University, New York.
* To whom correspondence should be addressed. E-mail: breslow{at}mail.rockefeller.edu.
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 µm2) and brachiocephalic artery (12 039±12 750 µm2) 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 µm2) and brachiocephalic arteries (125 666±59 339 µm2). 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 emphasizing the selection of diet to be used and the location of lesions to be scored.
Key words: atherosclerosis • mouse models • lipoproteins • nutrition • genetics
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