Cardiovascular Genomics pp 1-15 | Cite as
Modes of Defining Atherosclerosis in Mouse Models: Relative Merits and Evolving Standards
- 21 Citations
- 3.6k Downloads
Abstract
Mouse models have become the most common model for defining mechanisms of atherosclerotic disease. Many genetic manipulations have enabled the development of atherosclerosis in mice due to either endogenous or diet-induced hypercholesterolemia. This availability of lesion-susceptible mice has facilitated many studies using pharmacological and genetic approaches. Unfortunately, this expansive literature on mouse atherosclerosis has generated many contradictions on the role of specific pathways. A contributor to these inconsistencies may be the multiple modes in which atherosclerosis is evaluated. Also, for each specific technique, there are no consistent standards applied to the measurements. This chapter will discuss the imaging, biochemical, and compositional modes of evaluating atherosclerosis with suggestions for standard execution of these techniques.
Key words
Atherosclerosis mouse imaging cholesterolNotes
Acknowledgments
The authors’ laboratories are supported by the National Institutes of Health (HL08100 and HL62846).
References
- 1.Rader, DJ, Daugherty, A. (2008) Translating molecular discoveries into new therapies for atherosclerosis. Nature 451, 904–913.PubMedCrossRefGoogle Scholar
- 2.Daugherty, A. (2002) Mouse models of atherosclerosis. Am J Med Sci 323, 3–10.PubMedCrossRefGoogle Scholar
- 3.Schwartz, SM, Galis, ZS, Rosenfeld, ME, et al. (2007) Plaque rupture in humans and mice. Arterioscler Thromb Vasc Biol 27, 705–713.PubMedCrossRefGoogle Scholar
- 4.Jackson, CL, Bennett, MR, Biessen, EA, et al. (2007) Assessment of unstable atherosclerosis in mice. Arterioscler Thromb Vasc Biol 27, 714–720.PubMedCrossRefGoogle Scholar
- 5.Falk, E. (1999) Stable versus unstable atherosclerosis: clinical aspects. Am Heart J 138, S421–S425.PubMedCrossRefGoogle Scholar
- 6.Piedrahita, JA, Zhang, SH, Hagaman, JR, et al. (1992) Generation of mice carrying a mutant apolipoprotein-E gene inactivated by gene targeting in embryonic stem cells. Proc Natl Acad Sci USA 89, 4471–4475.PubMedCrossRefGoogle Scholar
- 7.Plump, AS, Smith, JD, Hayek, T, et al. (1992) Severe hypercholesterolemia and atherosclerosis in apolipoprotein-E-deficient mice created by homologous recombination in ES cells. Cell 71, 343–353.PubMedCrossRefGoogle Scholar
- 8.Ishibashi, S, Goldstein, JL, Brown, MS, et al. (1994) Massive xanthomatosis and atherosclerosis in cholesterol-fed low density lipoprotein receptor-negative mice. J Clin Invest 93, 1885–1893.PubMedCrossRefGoogle Scholar
- 9.Suzuki, H, Kurihara, Y, Takeya, M, et al. (1997) A role for macrophage scavenger receptors in atherosclerosis and susceptibility to infection. Nature 386, 292–296.PubMedCrossRefGoogle Scholar
- 10.Whitman, SC, Rateri, DL, Szilvassy, SJ, et al. (2002) Macrophage-specific expression of class A scavenger receptors in LDL receptor(–/–) mice decreases atherosclerosis and changes spleen morphology. J Lipid Res 43, 1201–1208.PubMedGoogle Scholar
- 11.Herijgers, N, de Winther, MP, Van Eck, M, et al. (2000) Effect of human scavenger receptor class A overexpression in bone marrow-derived cells on lipoprotein metabolism and atherosclerosis in low density lipoprotein receptor knockout mice. J Lipid Res 41, 1402–1409.PubMedGoogle Scholar
- 12.Daugherty, A, Whitman, SC, Block, AE, et al. (2000) Polymorphism of class A scavenger receptors in C57BL/6 mice. J Lipid Res 41, 1568–1577.PubMedGoogle Scholar
- 13.Witztum, JL. (2005) You are right too! J Clin Invest 115, 2072–2075.PubMedCrossRefGoogle Scholar
- 14.Curtiss, LK. (2006) Is two out of three enough for ABCG1? Arterioscler Thromb Vasc Biol 26, 2175–2177.PubMedCrossRefGoogle Scholar
- 15.Paigen, B, Morrow, A, Holmes, P, et al. (1987) Quantitative assessment of atherosclerotic lesions in mice. Atherosclerosis 68, 231–240.PubMedCrossRefGoogle Scholar
- 16.Daugherty, A, Whitman, SC. (2003) Quantification of atherosclerosis in mice. Methods Mol Biol 209, 293–309.PubMedGoogle Scholar
- 17.Baglione, J, Smith, JD. (2006) Quantitative assay for mouse atherosclerosis in the aortic root. Methods Mol Med 129, 83–95.PubMedGoogle Scholar
- 18.Purcell-Huynh, DA, Farese, RV, Johnson, DF, et al. (1995) Transgenic mice expressing high levels of human apolipoprotein B develop severe atherosclerotic lesions in response to a high-fat diet. J Clin Invest 95, 2246–2257.PubMedCrossRefGoogle Scholar
- 19.Tangirala, RK, Rubin, EM, Palinski, W. (1995) Quantitation of atherosclerosis in murine models: correlation between lesions in the aortic origin and in the entire aorta, and differences in the extent of lesions between sexes in LDL receptor-deficient and apolipoprotein E-deficient mice. J Lipid Res 36, 2320–2328.PubMedGoogle Scholar
- 20.Daugherty, A, Rateri, DL. (2005) Development of experimental designs for atherosclerosis studies in mice. Methods 36, 129–138.PubMedCrossRefGoogle Scholar
- 21.Nakashima, Y, Plump, AS, Raines, EW, et al. (1994) ApoE-deficient mice develop lesions of all phases of atherosclerosis throughout the arterial tree. Arterioscler Thromb 14, 133–140.PubMedCrossRefGoogle Scholar
- 22.Daugherty, A, Manning, MW, Cassis, LA. (2000) Angiotensin II promotes atherosclerotic lesions and aneurysms in apolipoprotein E-deficient mice. J Clin Invest 105, 1605–1612.PubMedCrossRefGoogle Scholar
- 23.Rosenfeld, ME, Polinsky, P, Virmani, R, et al. (2000) Advanced atherosclerotic lesions in the innominate artery of the ApoE knockout mouse. Arterioscler Thromb Vasc Biol 20, 2587–2592.PubMedCrossRefGoogle Scholar
- 24.Reardon, CA, Blachowicz, L, Lukens, J, et al. (2003) Genetic background selectively influences innominate artery atherosclerosis – Immune system deficiency as a probe. Arterioscler Thromb Vasc Biol 23, 1449–1454.PubMedCrossRefGoogle Scholar
- 25.Daugherty, A, Pure, E, Delfel-Butteiger, D, et al. (1997) The effects of total lymphocyte deficiency on the extent of atherosclerosis in apolipoprotein E –/– mice. J Clin Invest 100, 1575–1580.PubMedCrossRefGoogle Scholar
- 26.Lu, H, Rateri, DL, Daugherty, A. (2007) Immunostaining of mouse atherosclerotic lesions. Methods Mol Med 139, 77–94.PubMedCrossRefGoogle Scholar
- 27.Falk, E. (2006) Pathogenesis of atherosclerosis. J Am Coll Cardiol 47, C7–C12.PubMedCrossRefGoogle Scholar
- 28.Daugherty, A, Zweifel, BS, Schonfeld, G. (1991) The effects of probucol on the progression of atherosclerosis in mature Watanabe heritable hyperlipidaemic rabbits. Br J Pharmacol 103, 1013–1018.PubMedCrossRefGoogle Scholar
- 29.Fazio, S, Linton, MF. (1996) Murine bone marrow transplantation as a novel approach to studying the role of macrophages in lipoprotein metabolism and atherogenesis. Trends Cardiovasc Med 6, 58–65.PubMedCrossRefGoogle Scholar
- 30.Whitman, SC. (2004) A practical approach to using mice in atherosclerosis research. Clin Biochem Rev 25, 81–93.PubMedGoogle Scholar