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Journal of Lipid Research, Vol 36, 2320-2328, Copyright © 1995 by Lipid Research, Inc.
RK Tangirala, EM Rubin and W Palinski
Murine strains susceptible to atherosclerosis provide valuable models to
study factors involved in atherogenesis. In some murine models, limited
hypercholesterolemia can be achieved and lesions develop primarily in the
aortic origin, in the vicinity of the aortic valve. In other models such as
LDL receptor-deficient and apoE-deficient mice, diet-induced or spontaneous
hypercholesterolemia and atherogenesis are much greater. To determine
whether lesion formation in the aortic origin, where particular pathogenic
conditions may exist, correlates with lesion formation throughout the
entire aorta, we measured the extent of atherosclerosis in both areas in 8
apoE- and 11 LDL receptor- deficient mice fed cholesterol-rich diets for
3-6 months, as well as in 9 C57BL/6 mice fed an atherogenic diet for a
year, using two different morphometric methods. Both apoE-deficient and LDL
receptor-deficient mice developed extensive lesions throughout the aorta,
and in these models a significant correlation was observed between the
extent of lesions in the entire aorta (measured as percent of surface area)
and that at the aortic origin (measured as averaged lesion area per cross-
section) (r = 0.77, P < 0.0001). In contrast, the plasma cholesterol
levels achieved in C57BL/6 mice were much lower, and atherosclerotic
lesions were found almost exclusively in the aortic origin. These results
demonstrate that in murine models developing extensive aortic lesions, both
morphometric methods provide valid and complementary information on the
degree and distribution of atherosclerosis, and suggest that under severe
atherogenic conditions lesion formation throughout the aorta is determined
by the same pathological factors, in each model. Comparison of the extent
of atherosclerosis in the entire aorta between genders also showed that
male LDL receptor-deficient mice had significantly more lesions than
females (29.2 vs. 14.8%, P < 0.005, n = 16). A similar trend was also
seen in apoE-deficient mice.
ARTICLES
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
Department of Medicine, University of California, San Diego, La Jolla 92093-0682, USA.
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