Atherosclerosis in mice lacking apo E. Evaluation of lesional development and progression
Open accessAbstract
Apolipoprotein E-deficient mice have spontaneous elevations of total plasma cholesterol and triglycerides and reduced high-density lipoprotein. The mice develop arterial lesions in a time-dependent manner. Lesional distribution was centered in the aortic sinus in young mice, and the lesions were widely distributed throughout the arterial tree in mice at 8 to 9 months of age. In young mice, subendothelial foam cell deposits were present in the aortic sinus adjacent to valve-attachment sites. By 5 months of age, foam cell deposits, free cholesterol, and admixed smooth muscle cells composed the developing atherosclerotic lesions. After 8 to 9 months of age, the arterial lesions showed increased complexity, and fibrous cap lesions were present. Transmission electron microscopy showed foam cells, smooth muscle cells (both contractile and synthetic varieties), cellular debris, and acicular cholesterol deposits within the plaques. By scanning electron microscopy, subendothelial collections of foam cells were present within the aortic sinus and ascending aorta. The results show that the complexity of the atherosclerotic lesions that develop in these apo E deficient-mice are similar to those described in other species and therefore represent an important model for studies of genetic and environmental influences on the atherosclerotic process.
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Mutations in apoE that diminish binding of apoE-containing lipoproteins to the LDL receptor are associated with high plasma cholesterol levels and cause premature atherosclerosis in humans and experimental animals.
“In vivo and in vitro studies have shown that mutations in apoE that diminish binding of apoE-containing lipoproteins to the LDL receptor are associated with high plasma cholesterol levels and cause premature atherosclerosis in humans and experimental animals ( 1-3, 7, 8 ).”
From Molecular etiology of a dominant form of type III hyperlipoproteinemia caused by R142C substitution in apoE4 (2011) · cites this paper as [3]
The Abstract (p. 141) reports elevated plasma cholesterol and developing atherosclerotic lesions in apoE-deficient mice. The paper does not establish that apoE mutations diminish lipoprotein binding to the LDL receptor, or that such mutations cause premature atherosclerosis in humans. (LLM, conf=0.86)
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- Authors
- Reddick, R. L., Zhang, S. H., & Maeda, N.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- Venue
- Arteriosclerosis and Thrombosis: A Journal of Vascular Biology
- Published
- 1994-01
- Volume
- 14
- Issue
- 1
- Pages
- 141-147
- ISSN
- 1049-8834 (ISSN-L)
- OpenAlex
- W1859624620
- Cited by
- 633
- References
- 1
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 8 · 2023: 10 · 2022: 14 · 2021: 13 · 2020: 8 · 2019: 14 · 2018: 11 · 2017: 12 · 2016: 21 · 2015: 21 · 2014: 16 · 2013: 26 · 2012: 24
- FWCI
- 10.02
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Arteriosclerosis and Thrombosis A Journal of Vascular Biology (publishedVersion)
- PubMed (publishedVersion)
- Arteriosclerosis and Thrombosis A Journal of Vascular Biology
- Funders
- National Institutes of Health
- National Heart, Lung, and Blood Institute (HL 42630)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Keywords
- atherosclerosis, apolipoprotein E deficiency, ApoE-deficient mice, foam cells, free cholesterol, smooth muscle cells, fibrous cap, lesion progression, hypercholesterolemia, high-density lipoprotein, atherosclerosis model
- MeSH terms
- Aging, Animals, Aorta, Apolipoproteins E, Arteries, Arteriosclerosis, Cholesterol, Endothelium, Vascular, Mice, Inbred C57BL, Mice, Mutant Strains, Microscopy, Electron, Microscopy, Electron, Scanning, Muscle, Smooth, Vascular, Sinus of Valsalva, Triglycerides, Mice
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