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.


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 microm2) and brachiocephalic artery (12,039+/-12,750 microm2) 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 microm2) and brachiocephalic arteries (125,666+/-59,339 microm2). 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.
Teupser
Daniel
D
Laboratory of Biochemical Genetics and Metabolism, The Rockefeller University, New York, NY 10021, USA.
Persky
Adam D
AD
Breslow
Jan L
JL
D000704:Analysis of Variance; D000818:Animals; D001011:Aorta / Q000473:pathology*; D001161:Arteriosclerosis / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D016122:Brachiocephalic Trunk / Q000473:pathology*; D002784:Cholesterol / Q000097:blood*; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D018752:Diet, Fat-Restricted; D004195:Disease Models, Animal; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D011973:Receptors, LDL / Q000172:deficiency / Q000235:genetics; D013045:Species Specificity; D014280:Triglycerides / Q000097:blood
D002791:Cholesterol, Dietary; D011973:Receptors, LDL; D014280:Triglycerides; D002784:Cholesterol