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Modes of Defining Atherosclerosis in Mouse Models: Relative Merits and Evolving Standards

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Cardiovascular Genomics

Part of the book series: Methods in Molecular Biology™ ((MIMB,volume 573))

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.

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References

  1. Rader, DJ, Daugherty, A. (2008) Translating molecular discoveries into new therapies for atherosclerosis. Nature 451, 904–913.

    Article  PubMed  CAS  Google Scholar 

  2. Daugherty, A. (2002) Mouse models of atherosclerosis. Am J Med Sci 323, 3–10.

    Article  PubMed  Google Scholar 

  3. Schwartz, SM, Galis, ZS, Rosenfeld, ME, et al. (2007) Plaque rupture in humans and mice. Arterioscler Thromb Vasc Biol 27, 705–713.

    Article  PubMed  CAS  Google Scholar 

  4. Jackson, CL, Bennett, MR, Biessen, EA, et al. (2007) Assessment of unstable atherosclerosis in mice. Arterioscler Thromb Vasc Biol 27, 714–720.

    Article  PubMed  CAS  Google Scholar 

  5. Falk, E. (1999) Stable versus unstable atherosclerosis: clinical aspects. Am Heart J 138, S421–S425.

    Article  PubMed  CAS  Google 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.

    Article  PubMed  CAS  Google 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.

    Article  PubMed  CAS  Google 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.

    Article  PubMed  CAS  Google 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.

    Article  PubMed  CAS  Google 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.

    PubMed  CAS  Google 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.

    PubMed  CAS  Google 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.

    PubMed  CAS  Google Scholar 

  13. Witztum, JL. (2005) You are right too! J Clin Invest 115, 2072–2075.

    Article  PubMed  CAS  Google Scholar 

  14. Curtiss, LK. (2006) Is two out of three enough for ABCG1? Arterioscler Thromb Vasc Biol 26, 2175–2177.

    Article  PubMed  CAS  Google Scholar 

  15. Paigen, B, Morrow, A, Holmes, P, et al. (1987) Quantitative assessment of atherosclerotic lesions in mice. Atherosclerosis 68, 231–240.

    Article  PubMed  CAS  Google Scholar 

  16. Daugherty, A, Whitman, SC. (2003) Quantification of atherosclerosis in mice. Methods Mol Biol 209, 293–309.

    PubMed  Google Scholar 

  17. Baglione, J, Smith, JD. (2006) Quantitative assay for mouse atherosclerosis in the aortic root. Methods Mol Med 129, 83–95.

    PubMed  CAS  Google 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.

    Article  PubMed  CAS  Google 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.

    PubMed  CAS  Google Scholar 

  20. Daugherty, A, Rateri, DL. (2005) Development of experimental designs for atherosclerosis studies in mice. Methods 36, 129–138.

    Article  PubMed  CAS  Google 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.

    Article  PubMed  CAS  Google 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.

    Article  PubMed  CAS  Google 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.

    Article  PubMed  CAS  Google 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.

    Article  PubMed  CAS  Google 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.

    Article  PubMed  CAS  Google Scholar 

  26. Lu, H, Rateri, DL, Daugherty, A. (2007) Immunostaining of mouse atherosclerotic lesions. Methods Mol Med 139, 77–94.

    Article  PubMed  CAS  Google Scholar 

  27. Falk, E. (2006) Pathogenesis of atherosclerosis. J Am Coll Cardiol 47, C7–C12.

    Article  PubMed  CAS  Google 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.

    Article  PubMed  CAS  Google 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.

    Article  PubMed  CAS  Google Scholar 

  30. Whitman, SC. (2004) A practical approach to using mice in atherosclerosis research. Clin Biochem Rev 25, 81–93.

    PubMed  Google Scholar 

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Acknowledgments

The authors’ laboratories are supported by the National Institutes of Health (HL08100 and HL62846).

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© 2009 Humana Press, a part of Springer Science+Business Media, LLC

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Daugherty, A., Lu, H., Howatt, D.A., Rateri, D.L. (2009). Modes of Defining Atherosclerosis in Mouse Models: Relative Merits and Evolving Standards. In: DiPetrillo, K. (eds) Cardiovascular Genomics. Methods in Molecular Biology™, vol 573. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60761-247-6_1

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  • DOI: https://doi.org/10.1007/978-1-60761-247-6_1

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  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-60761-246-9

  • Online ISBN: 978-1-60761-247-6

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