Abstract
The mouse has become the preferred species for genetic manipulation aimed at creating and studying models for human disease. Although mice are highly resistant to atherosclerosis, dietary induction and, more frequently, gene knockout and transgenic mice have been widely used to study factors that alter the susceptibility to atherosclerosis. Although there are several ways to assess atherosclerosis in mice, measurement of the aortic root lesion area is a commonly used, medium-throughput method that allows for histological examination of the lesions. Here, we provide the detailed methods for the quantitative analysis of mouse aortic root lesion area.
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References
Smith, J. D. and Breslow, J. L. (1997) The emergence of mouse models of atherosclerosis and their relevance to clinical research. J. Intern. Med. 242, 99–109.
Paigen, B., Havens, M. B., and Morrow, A. (1985) Effect of 3-methylcholanthrene on the development of aortic lesions in mice. Cancer Res. 45, 3850–3855.
Paigen, B., Morrow, A., Brandon, C., Mitchell, D., and Holmes, P. (1985) Variation in susceptibility to atherosclerosis among inbred strains of mice. Atherosclerosis 57, 65–73.
Paigen, B., Morrow, A., Holmes, P. A., Mitchell, D., and Williams, R. A. (1987) Quantitative assessment of atherosclerotic lesions in mice. Atherosclerosis 68, 231–240.
Paigen, B., Mitchell, D., Reue, K., Morrow, A., Lusis, A. J., and LeBoeuf, R. C. (1987) Ath-1, a gene determining atherosclerosis susceptibility and high density lipoprotein levels in mice. Proc. Natl. Acad. Sci. USA 84, 3763–3767.
Wang, X., Ria, M., Kelmenson, P. M., et al. (2005) Positional identification of TNFSF4, encoding OX40 ligand, as a gene that influences atherosclerosis susceptibility. Nat. Genet. 37, 365–372.
Plump, A. S., Smith, J. D., 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.
Zhang, S. H., Reddick, R. L., Piedrahita, J. A., and Maeda, N. (1992) Spontaneous hypercholesterolemia and arterial lesions in mice lacking apolipoprotein E. Science 258, 468–471.
Ishibashi, S., Brown, M. S., Goldstein, J. L., Gerard, R. D., Hammer, R. E., and Herz, J. (1993) Hypercholesterolemia in low density lipoprotein receptor knockout mice and its reversal by adenovirus-mediated gene delivery. J. Clin. Invest. 92, 883–893.
Tangirala, R. K., Rubin, E. M., and 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.
Febbraio, M., Podrez, E. A., Smith, J. D., et al. (2000) Targeted disruption of the class B scavenger receptor CD36 protects against atherosclerotic lesion development in mice. J Clin. Invest 105, 1049–1056.
Lichtman, A. H., Clinton, S. K., Iiyama, K., Connelly, P. W., Libby, P., and Cybulsky, M. I. (1999) Hyperlipidemia and atherosclerotic lesion development in LDL receptor-deficient mice fed defined semipurified diets with and without cholate. Arterioscler. Thromb. Vasc. Biol. 19, 1938–1944.
Rudel, L. L., Kelley, K., Sawyer, J. K., Shah, R., and Wilson, M. D. (1998) Dietary monounsaturated fatty acids promote aortic atherosclerosis in LDL receptor-null, human ApoB100-overexpressing transgenic mice. Arterioscler. Thromb. Vasc. Biol. 18, 1818–1827.
Nakashima, Y., Plump, A. S., Raines, E. W., Breslow, J. L., and Ross, R. (1994) ApoE-deficient mice develop lesions of all phases of atherosclerosis throughout the arterial tree. Arterioscler. Thromb. 14, 133–140.
Seo, H. S., Lombardi, D. M., Polinsky, P., et al. (1997) Peripheral vascular stenosis in apolipoprotein E-deficient mice. Potential roles of lipid deposition, medial atrophy, and adventitial inflammation. Arterioscler. Thromb. Vasc. Biol. 17, 3593–3601.
Rosenfeld, M. E., Kauser, K., Martin-McNulty, B., Polinsky, P., Schwartz, S. M., and Rubanyi, G. M. (2002) Estrogen inhibits the initiation of fatty streaks throughout the vasculature but does not inhibit intra-plaque hemorrhage and the progression of established lesions in apolipoprotein E deficient mice. Atherosclerosis 164, 251–259.
VanderLaan, P. A., Reardon, C. A., and Getz, G. S. (2004) Site specificity of atherosclerosis: site-selective responses to atherosclerotic modulators. Arterioscler. Thromb. Vasc. Biol. 24, 12–22.
Daugherty, A. and Whitman, S. C. (2003) Quantification of atherosclerosis in mice, Methods Mol. Biol. 209, 293–309.
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Baglione, J., Smith, J.D. (2006). Quantitative Assay for Mouse Atherosclerosis in the Aortic Root. In: Wang, Q.K. (eds) Cardiovascular Disease. Methods in Molecular Medicine, vol 129. Humana Press. https://doi.org/10.1385/1-59745-213-0:83
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DOI: https://doi.org/10.1385/1-59745-213-0:83
Publisher Name: Humana Press
Print ISBN: 978-1-58829-892-8
Online ISBN: 978-1-59745-213-7
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