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Increased Atherosclerosis in Hyperlipidemic Mice With Inactivation of ABCA1 in Macrophages
Open accessAbstract
The ATP-binding cassette transporter A1 (ABCA1) encodes a membrane protein that promotes cholesterol and phospholipid efflux from cells. Mutations in ABCA1 lead to HDL deficiency and tissue accumulation of macrophages in patients with homozygous Tangier disease. In this study, we examined whether the complete absence of ABCA1 or selected inactivation in macrophages is accompanied by an increase in atherosclerotic lesion progression in hypercholesterolemic apolipoprotein E–deficient (apoE −/− ) mice and LDLR receptor–deficient (LDLr −/− ) mice. The absence of ABCA1 led to reduced plasma cholesterol levels in both the apoE −/− and LDLr −/− mice, along with severe skin xanthomatosis characterized by marked foamy macrophages and cholesterol ester accumulation. However, the complete absence of ABCA1 did not affect the development, progression, or composition of atherosclerotic lesions in either the LDLr −/− or the apoE −/− mice fed a chow or atherogenic diet. In contrast, bone marrow transplantation studies demonstrated that the selective inactivation of ABCA1 in macrophages markedly increased atherosclerosis and foam cell accumulation in apoE −/− . Taken together, these findings demonstrate that the complete absence of ABCA1 has a major impact on plasma lipoprotein homeostasis, and the proposed antiatherogenic effect resulting from ABCA1 deficiency is compensated by a less atherogenic profile. ABCA1 deficiency in macrophages, however, demonstrates the antiatherogenic properties of ABCA1 independent of plasma lipids and HDL levels.
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“Cholesterol efflux from cells to apolipoprotein A-I (apoA-I) acceptors via the ATP-binding cassette transporters ABCA1 and ABCG1 is thought to be central in the antiatherogenic mechanism.”
From MicroRNA‐33 Deficiency Reduces the Progression of Atherosclerotic Plaque in ApoE −/− Mice (2012) · cites this paper as [10]
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“Studies in mice in which the Abca1 locus is either deleted or overexpressed generally have supported the hypothesis that ABCA1 significantly prevents atherosclerosis by maintaining circulating HDL-C levels and cellular cholesterol efflux.10–13”
From MicroRNA‐33 Deficiency Reduces the Progression of Atherosclerotic Plaque in ApoE −/− Mice (2012) · cites this paper as [10]
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Metadata
- Authors
- Aiello, R. J., Brees, D., Bourassa, P.-A., Royer, L., Lindsey, S., Coskran, T., Haghpassand, M., & Francone, O. L.
- Affiliations
- Pfizer (United States) (US)
- Venue
- Arteriosclerosis, Thrombosis, and Vascular Biology
- Published
- 2002-04
- Volume
- 22
- Issue
- 4
- Pages
- 630-637
- ISSN
- 1079-5642 (ISSN-L)
- 1524-4636
- OpenAlex
- W2128738849
- Cited by
- 390
- References
- 38
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 3 · 2023: 2 · 2022: 10 · 2021: 11 · 2020: 8 · 2019: 6 · 2018: 9 · 2017: 14 · 2016: 11 · 2015: 19 · 2014: 22 · 2013: 17 · 2012: 20
- FWCI
- 30.15
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Arteriosclerosis Thrombosis and Vascular Biology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
- Keywords
- ABCA1, atherosclerosis, macrophages, hyperlipidemia, Tangier disease, HDL deficiency, ApoE-deficient mice, LDL receptor-deficient mice, foam cells, xanthomatosis, cholesterol efflux, bone marrow transplantation, atherogenic diet
- MeSH terms
- Animals, Apolipoproteins E, Arteriosclerosis, Cholesterol, Crosses, Genetic, Female, Hyperlipidemias, Lipids, Lipoproteins, Macrophages, Male, Mice, Inbred C57BL, Mice, Inbred DBA, Receptors, LDL, Xanthomatosis, Bone Marrow Transplantation, ATP-Binding Cassette Transporters, Mice, ATP Binding Cassette Transporter 1
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