Published online before print August 7, 2003, doi: 10.1161/01.ATV.0000090126.34881.B1
© 2003 American Heart Association, Inc.
Atherosclerosis and Lipoproteins |
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)
From the Laboratory of Biochemical Genetics and Metabolism, The Rockefeller University, New York.
Address correspondence to Jan L. Breslow, The Rockefeller University, Laboratory of Biochemical Genetics and Metabolism, RU Box 179, 1230 York Ave, New York, NY 10021. 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 informing the selection of diet to be used and the location of lesions to be scored.
Key Words: atherosclerosis • mouse models • lipoproteins • nutrition • genetics
This article has been cited by other articles:
 |
|
 |
|
  M.-S. Kuo, J. M. Kalbfleisch, P. Rutherford, D. Gifford-Moore, X.-d. Huang, R. Christie, K. Hui, K. Gould, and M. Rekhter Chemical analysis of atherosclerotic plaque cholesterol combined with histology of the same tissue J. Lipid Res., June 1, 2008; 49(6): 1353 - 1363. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. M. Holdt, J. Thiery, J. L. Breslow, and D. Teupser Increased ADAM17 mRNA Expression and Activity Is Associated With Atherosclerosis Resistance in LDL-Receptor Deficient Mice Arterioscler. Thromb. Vasc. Biol., June 1, 2008; 28(6): 1097 - 1103. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. J. Goldberg, Y. Hu, H.-L. Noh, J. Wei, L. A. Huggins, M. G. Rackmill, H. Hamai, B. N. Reid, W. S. Blaner, and L.-S. Huang Decreased Lipoprotein Clearance Is Responsible for Increased Cholesterol in LDL Receptor Knockout Mice With Streptozotocin-Induced Diabetes Diabetes, June 1, 2008; 57(6): 1674 - 1682. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Christoffersen, M. Jauhiainen, M. Moser, B. Porse, C. Ehnholm, M. Boesl, B. Dahlback, and L. B. Nielsen Effect of Apolipoprotein M on High Density Lipoprotein Metabolism and Atherosclerosis in Low Density Lipoprotein Receptor Knock-out Mice J. Biol. Chem., January 25, 2008; 283(4): 1839 - 1847. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Wolfrum, D. Teupser, M. Tan, K. Y. Chen, and J. L. Breslow The protective effect of A20 on atherosclerosis in apolipoprotein E-deficient mice is associated with reduced expression of NF-{kappa}B target genes PNAS, November 20, 2007; 104(47): 18601 - 18606. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Thorp, G. Kuriakose, Y. M. Shah, F. J. Gonzalez, and I. Tabas Pioglitazone Increases Macrophage Apoptosis and Plaque Necrosis in Advanced Atherosclerotic Lesions of Nondiabetic Low-Density Lipoprotein Receptor Null Mice Circulation, November 6, 2007; 116(19): 2182 - 2190. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. S. Wang, E. E. Schadt, H. Wang, X. Wang, L. Ingram-Drake, W. Shi, T. A. Drake, and A. J. Lusis Identification of Pathways for Atherosclerosis in Mice: Integration of Quantitative Trait Locus Analysis and Global Gene Expression Data Circ. Res., August 3, 2007; 101(3): e11 - e30. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Hsueh, E. D. Abel, J. L. Breslow, N. Maeda, R. C. Davis, E. A. Fisher, H. Dansky, D. A. McClain, R. McIndoe, M. K. Wassef, et al. Recipes for Creating Animal Models of Diabetic Cardiovascular Disease Circ. Res., May 25, 2007; 100(10): 1415 - 1427. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Hartvigsen, C. J. Binder, L. F. Hansen, A. Rafia, J. Juliano, S. Horkko, D. Steinberg, W. Palinski, J. L. Witztum, and A. C. Li A Diet-Induced Hypercholesterolemic Murine Model to Study Atherogenesis Without Obesity and Metabolic Syndrome Arterioscler. Thromb. Vasc. Biol., April 1, 2007; 27(4): 878 - 885. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Freeman, M. J. A. Amar, R. Shamburek, B. Paigen, H. B. Brewer Jr., S. Santamarina-Fojo, and H. Gonzalez-Navarro Lipolytic and ligand-binding functions of hepatic lipase protect against atherosclerosis in LDL receptor-deficient mice J. Lipid Res., January 1, 2007; 48(1): 104 - 113. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Plat, I. Beugels, M. J. J. Gijbels, M. P. J. de Winther, and R. P. Mensink Plant sterol or stanol esters retard lesion formation in LDL receptor-deficient mice independent of changes in serum plant sterols J. Lipid Res., December 1, 2006; 47(12): 2762 - 2771. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Wu, R. Vikramadithyan, S. Yu, C. Pau, Y. Hu, I. J. Goldberg, and H. M. Dansky Addition of dietary fat to cholesterol in the diets of LDL receptor knockout mice: effects on plasma insulin, lipoproteins, and atherosclerosis J. Lipid Res., October 1, 2006; 47(10): 2215 - 2222. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Teupser, R. Burkhardt, W. Wilfert, I. Haffner, K. Nebendahl, and J. Thiery Identification of Macrophage Arginase I as a New Candidate Gene of Atherosclerosis Resistance Arterioscler. Thromb. Vasc. Biol., February 1, 2006; 26(2): 365 - 371. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. S. Getz and C. A. Reardon Diet and Murine Atherosclerosis Arterioscler. Thromb. Vasc. Biol., February 1, 2006; 26(2): 242 - 249. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Teupser, M. Tan, A. D. Persky, and J. L. Breslow Atherosclerosis quantitative trait loci are sex- and lineage-dependent in an intercross of C57BL/6 and FVB/N low-density lipoprotein receptor-/- mice PNAS, January 3, 2006; 103(1): 123 - 128. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. P.W. Moos, N. John, R. Grabner, S. Nossmann, B. Gunther, R. Vollandt, C. D. Funk, B. Kaiser, and A. J.R. Habenicht The Lamina Adventitia Is the Major Site of Immune Cell Accumulation in Standard Chow-Fed Apolipoprotein E-Deficient Mice Arterioscler. Thromb. Vasc. Biol., November 1, 2005; 25(11): 2386 - 2391. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. R. Hojjati, Z. Li, H. Zhou, S. Tang, C. Huan, E. Ooi, S. Lu, and X.-C. Jiang Effect of Myriocin on Plasma Sphingolipid Metabolism and Atherosclerosis in apoE-deficient Mice J. Biol. Chem., March 18, 2005; 280(11): 10284 - 10289. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. S. Getz Thematic review series: The Immune System and Atherogenesis. Immune function in atherogenesis J. Lipid Res., January 1, 2005; 46(1): 1 - 10. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Sehayek and J. L. Breslow Plasma Plant Sterol Levels: Another Coronary Heart Disease Risk Factor? Arterioscler. Thromb. Vasc. Biol., January 1, 2005; 25(1): 5 - 6. [Full Text] [PDF]
|
|
|
|
|
|
D. Teupser, S. Pavlides, M. Tan, J.-C. Gutierrez-Ramos, R. Kolbeck, and J. L. Breslow Major reduction of atherosclerosis in fractalkine (CX3CL1)-deficient mice is at the brachiocephalic artery, not the aortic root PNAS, December 21, 2004; 101(51): 17795 - 17800. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. J. Lusis, A. M. Fogelman, and G. C. Fonarow Genetic Basis of Atherosclerosis: Part II: Clinical Implications Circulation, October 5, 2004; 110(14): 2066 - 2071. [Full Text] [PDF]
|
|