Increased atherosclerosis in mice reconstituted with apolipoprotein E null macrophages
Open accessAbstract
Macrophage-derived foam cells express apolipoprotein E (apoE) abundantly in atherosclerotic lesions. To examine the physiologic role of apoE secretion by the macrophage in atherogenesis, bone marrow transplantation was used to reconstitute C57BL/6 mice with macrophages that were either null or wild type for the apoE gene. After 13 weeks on an atherogenic diet, C57BL/6 mice reconstituted with apoE null marrow developed 10-fold more atherosclerosis than controls in the absence of significant differences in serum cholesterol levels or lipoprotein profiles. ApoE expression was absent in the macrophage-derived foam cells of C57BL/6 mice reconstituted with apoE null marrow. Thus, lack of apoE expression by the macrophage promotes foam cell formation. These data support a protective role for apoE expression by the macrophage in early atherogenesis.
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apoE was the first apoprotein studied in murine BMT experiments, and has been shown to affect atherosclerosis both by reducing serum lipid levels and by exerting local beneficial effects in the forming atheroma.
“apoE was the fi rst apoprotein studied in murine BMT experiments, and has been shown to affect atherosclerosis both by reducing serum lipid levels ( 11 ) and by exerting local benefi cial effects in the forming atheroma ( 43 ).”
From Macrophage-derived apoESendai suppresses atherosclerosis while causing lipoprotein glomerulopathy in hyperlipidemic mice (2014) · cites this paper as [43]
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- Authors
- Fazio, S., Babaev, V. R., Murray, A. B., Hasty, A. H., Carter, K. J., Gleaves, L. A., Atkinson, J. B., & Linton, M. F.
- Affiliations
- Vanderbilt University (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1997-04-29
- Volume
- 94
- Issue
- 9
- Pages
- 4647-4652
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC20778
- OpenAlex
- W1992980650
- Cited by
- 295
- References
- 2
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 4 · 2023: 3 · 2022: 4 · 2021: 5 · 2020: 8 · 2019: 6 · 2018: 6 · 2017: 7 · 2016: 4 · 2015: 14 · 2014: 11 · 2013: 10 · 2012: 7
- FWCI
- 24.14
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Keywords
- apolipoprotein E, macrophages, atherosclerosis, foam cells, atherogenesis, bone marrow transplantation, atherogenic diet, C57BL/6 mice, ApoE-null mice
- MeSH terms
- Animals, Aorta, Apolipoproteins E, Arteriosclerosis, Cholesterol, Diet, Atherogenic, Female, Lipoproteins, Macrophages, Mice, Inbred C57BL, Mice, Mutant Strains, Bone Marrow Transplantation, Mice
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