Cited by 1,693Atherosclerosis and Cardiovascular DiseasesCholesterol and Lipid MetabolismLipoproteins and Cardiovascular Health

ApoE-deficient mice develop lesions of all phases of atherosclerosis throughout the arterial tree.

Nakashima, Y, Plump, A S, Raines, E W, Breslow, J L, Ross, R·1994·Arteriosclerosis and Thrombosis: A Journal of Vascular Biology

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.

Integrity signals

Registry

Crossref · 10.1161/01.atv.14.1.133

Cites

28 of 28 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • 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).”

Cites

Flagged first, then by citations

Cited by

Sorted by citations

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

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review