ApoE-deficient mice develop lesions of all phases of atherosclerosis throughout the arterial tree.
Abstract
Initial description of apolipoprotein (apo) E-deficient transgenic mice demonstrated the development of severe hypercholesterolemia due to probable delayed clearance of large atherogenic particles from the circulation. Examination of these mice demonstrated foam cell accumulation in the aortic root and pulmonary arteries by 10 weeks of age. In the present study, the animals were fed either chow or a high-fat, Western-type diet and examined at ages ranging from 6 to 40 weeks. Gross examination by dissection microscopy revealed a predilection for development of lesions in the aortic root, at the lesser curvature of the aortic arch, the principal branches of the aorta, and in the pulmonary and carotid arteries. Monocyte attachment to endothelial cells was observed by light and electron microscopic examination at 6 weeks, the earliest time point examined. Foam cell lesions developed as early as 8 weeks, and after 15 weeks advanced lesions (fibrous plaques) were observed. The latter consisted of a fibrous cap containing smooth muscle cells surrounded by connective tissue matrix that covered a necrotic core with numerous foamy macrophages. Mice fed the Western-type diet generally had more advanced lesions than those fed a chow diet. The apoE-deficient mouse contains the entire spectrum of lesions observed during atherogenesis and is the first mouse model to develop lesions similar to those in humans. This model should provide numerous opportunities to study the pathogenesis and therapy of atherosclerosis in a small, genetically defined animal.
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Apo E knockout mice are considered one of the most relevant models for atherosclerosis because they are hypercholesterolemic and develop spontaneous arterial lesions.
“Apo E knockout mice are considered to be one of the most relevant models for atherosclerosis because they are hypercholesterolemic and develop spontaneous arterial lesions (87).”
From Trimethylamine <i>N</i> -Oxide, the Microbiome, and Heart and Kidney Disease (2017) · cites this paper as [87]
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- Authors
- Nakashima, Y., Plump, A. S., Raines, E. W., Breslow, J. L., & Ross, R.
- Affiliations
- University of Washington (US)
- Venue
- Arteriosclerosis and Thrombosis: A Journal of Vascular Biology
- Published
- 1994-01
- Volume
- 14
- Issue
- 1
- Pages
- 133-140
- ISSN
- 1049-8834 (ISSN-L)
- OpenAlex
- W1964814612
- Cited by
- 1,693
- References
- 28
- Citations by year
- 2026: 18 · 2025: 32 · 2024: 40 · 2023: 42 · 2022: 54 · 2021: 60 · 2020: 47 · 2019: 57 · 2018: 45 · 2017: 66 · 2016: 50 · 2015: 69 · 2014: 71 · 2013: 73 · 2012: 78
- FWCI
- 14.99
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Arteriosclerosis and Thrombosis A Journal of Vascular Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Bristol-Myers Squibb
- National Institutes of Health (5r01hl033714-17, 18645, HL 18645)
- National Heart, Lung, and Blood Institute (HL-18645, HL 33714, R01HL032435, HL32435, P01HL018645)
- 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
- apolipoprotein E deficiency, atherosclerosis, atherosclerotic plaque development, Western diet, hypercholesterolemia, fibrous cap, necrotic core, aortic root lesions, mouse model of atherosclerosis, atherogenesis
- MeSH terms
- Animals, Aorta, Aorta, Thoracic, Apolipoproteins E, Arteriosclerosis, Carotid Arteries, Coronary Vessels, Diet, Endothelium, Vascular, Hypercholesterolemia, Leukocytes, Mononuclear, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Transgenic, Microscopy, Electron, Pulmonary Artery, Mice
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