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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)

Authors Daniel Teupser, Adam D. Persky, Jan L. Breslow Submitted By Birgit Kantor on 10/17/2003 Status Published Journal Arteriosclerosis, thrombosis, and vascular biology Year 2003 Date Published 10/1/2003 Volume : Pages 23(10) : 1907 - 1913 PubMed Reference 12907460 Abstract 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, Adam D. Persky, Jan L. Breslow 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 m2) and brachiocephalic artery (12 039 12 750 m2) 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 m2) and brachiocephalic arteries (125 666 59 339 m2). 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. (Arterioscler Thromb Vasc Biol. 2003;23:1907-1913.) Key Words: atherosclerosis mouse models lipoproteins nutrition genetics

Investigators with authorship
Name Institution Jan Breslow Rockefeller University

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