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Science 16 October 1992:
Vol. 258. no. 5081, pp. 468 - 471
DOI: 10.1126/science.1411543
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Articles

Science, Vol 258, Issue 5081, 468-471
Copyright © 1992 by American Association for the Advancement of Science

articles

Spontaneous hypercholesterolemia and arterial lesions in mice lacking apolipoprotein E

SH Zhang, RL Reddick, JA Piedrahita, and N Maeda

Department of Pathology, University of North Carolina, Chapel Hill 27599-7525.

Apolipoprotein E (apoE) is a ligand for receptors that clear remnants of chylomicrons and very low density lipoproteins. Lack of apoE is, therefore, expected to cause accumulation in plasma of cholesterol-rich remnants whose prolonged circulation should be atherogenic. ApoE-deficient mice generated by gene targeting were used to test this hypothesis and to make a mouse model for spontaneous atherosclerosis. The mutant mice had five times normal plasma cholesterol, and developed foam cell-rich depositions in their proximal aortas by age 3 months. These spontaneous lesions progressed and caused severe occlusion of the coronary artery ostium by 8 months. The severe yet viable phenotype of the mutants should make them valuable for investigating genetic and environmental factors that modify the atherogenic process.


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Hepatic Lipase Deficiency Delays Atherosclerosis, Myocardial Infarction, and Cardiac Dysfunction and Extends Lifespan in SR-BI/Apolipoprotein E Double Knockout Mice.
S. L. Karackattu, B. Trigatti, and M. Krieger (2006)
Arterioscler Thromb Vasc Biol 26, 548-554
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Quantitative Trait Locus Analysis of Atherosclerosis in an Intercross Between C57BL/6 and C3H Mice Carrying the Mutant Apolipoprotein E Gene.
Z. Su, Y. Li, J. C. James, M. McDuffie, A. H. Matsumoto, G. A. Helm, J. L. Weber, A. J. Lusis, and W. Shi (2006)
Genetics 172, 1799-1807
   Abstract »    Full Text »    PDF »
Diet and Murine Atherosclerosis.
G. S. Getz and C. A. Reardon (2006)
Arterioscler Thromb Vasc Biol 26, 242-249
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Antiatherogenic Effects of Angiotensin Receptor Antagonism in Mild Renal Dysfunction.
E. Suganuma, Y. Zuo, N. Ayabe, J. Ma, V. R. Babaev, M. F. Linton, S. Fazio, I. Ichikawa, A. B. Fogo, and V. Kon (2006)
J. Am. Soc. Nephrol. 17, 433-441
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Atherosclerosis quantitative trait loci are sex- and lineage-dependent in an intercross of C57BL/6 and FVB/N low-density lipoprotein receptor-/- mice.
D. Teupser, M. Tan, A. D. Persky, and J. L. Breslow (2006)
PNAS 103, 123-128
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Function of cGMP-Dependent Protein Kinases as Revealed by Gene Deletion.
F. Hofmann, R. Feil, T. Kleppisch, and J. Schlossmann (2006)
Physiol Rev 86, 1-23
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Inducible Nitric Oxide Synthase Mediates Prostaglandin H2 Synthase Nitration and Suppresses Eicosanoid Production.
R. S. Deeb, H. Shen, C. Gamss, T. Gavrilova, B. D. Summers, R. Kraemer, G. Hao, S. S. Gross, M. Laine, N. Maeda, et al. (2006)
Am. J. Pathol. 168, 349-362
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Expression of Neutrophil Gelatinase-Associated Lipocalin in Atherosclerosis and Myocardial Infarction.
A.-L. Hemdahl, A. Gabrielsen, C. Zhu, P. Eriksson, U. Hedin, J. Kastrup, P. Thoren, and G. K. Hansson (2006)
Arterioscler Thromb Vasc Biol 26, 136-142
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Endothelial lipase modulates HDL but has no effect on atherosclerosis development in apoE-/- and LDLR-/- mice.
K. W. S. Ko, A. Paul, K. Ma, L. Li, and L. Chan (2005)
J. Lipid Res. 46, 2586-2594
   Abstract »    Full Text »    PDF »
Molecular evidence for arterial repair in atherosclerosis.
R. Karra, S. Vemullapalli, C. Dong, E. E. Herderick, X. Song, K. Slosek, J. R. Nevins, M. West, P. J. Goldschmidt-Clermont, and D. Seo (2005)
PNAS 102, 16789-16794
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Nonparticulate Components of Diesel Exhaust Promote Constriction in Coronary Arteries from ApoE-/- Mice.
M. J. Campen, N. S. Babu, G. A. Helms, S. Pett, J. Wernly, R. Mehran, and J. D. McDonald (2005)
Toxicol. Sci. 88, 95-102
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Proteomic and Metabolomic Analyses of Atherosclerotic Vessels From Apolipoprotein E-Deficient Mice Reveal Alterations in Inflammation, Oxidative Stress, and Energy Metabolism.
M. Mayr, Y.-L. Chung, U. Mayr, X. Yin, L. Ly, H. Troy, S. Fredericks, Y. Hu, J. R. Griffiths, and Q. Xu (2005)
Arterioscler Thromb Vasc Biol 25, 2135-2142
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Chronic Mild Reduction of Cerebral Perfusion Pressure Induces Ischemic Tolerance in Focal Cerebral Ischemia.
K. Kitagawa, Y. Yagita, T. Sasaki, S. Sugiura, E. Omura-Matsuoka, T. Mabuchi, K. Matsushita, and M. Hori (2005)
Stroke 36, 2270-2274
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USF1 and dyslipidemias: converging evidence for a functional intronic variant.
J. Naukkarinen, M. Gentile, A. Soro-Paavonen, J. Saarela, H. A. Koistinen, P. Pajukanta, M.-R. Taskinen, and L. Peltonen (2005)
Hum. Mol. Genet. 14, 2595-2605
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Anti-Heat Shock Protein 60 Autoantibodies Induce Atherosclerosis in Apolipoprotein E-Deficient Mice via Endothelial Damage.
G. Foteinos, A. R. Afzal, K. Mandal, M. Jahangiri, and Q. Xu (2005)
Circulation 112, 1206-1213
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11{beta}-HSD1 inhibition ameliorates metabolic syndrome and prevents progression of atherosclerosis in mice.
A. Hermanowski-Vosatka, J. M. Balkovec, K. Cheng, H. Y. Chen, M. Hernandez, G. C. Koo, C. B. Le Grand, Z. Li, J. M. Metzger, S. S. Mundt, et al. (2005)
J. Exp. Med. 202, 517-527
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Role of C-Reactive Protein in Atherogenesis: Can the Apolipoprotein E Knockout Mouse Provide the Answer?.
K. Reifenberg, H.-A. Lehr, D. Baskal, E. Wiese, S. C. Schaefer, S. Black, D. Samols, M. Torzewski, K. J. Lackner, M. Husmann, et al. (2005)
Arterioscler Thromb Vasc Biol 25, 1641-1646
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Age-Associated Aortic Stenosis in Apolipoprotein E-Deficient Mice.
K. Tanaka, M. Sata, D. Fukuda, Y. Suematsu, N. Motomura, S. Takamoto, Y. Hirata, and R. Nagai (2005)
J. Am. Coll. Cardiol. 46, 134-141
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