Cited by 390Cholesterol and Lipid MetabolismAtherosclerosis and Cardiovascular DiseasesLipoproteins and Cardiovascular Health

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Increased Atherosclerosis in Hyperlipidemic Mice With Inactivation of ABCA1 in Macrophages

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Aiello, Robert J., Brees, Dominique, Bourassa, Patricia-Ann, Royer, Lori, Lindsey, Saralyn, Coskran, Timothy, Haghpassand, Mehrdad, Francone, Omar L.·2002·Arteriosclerosis, Thrombosis, and Vascular Biology

DOI 10.1161/01.atv.0000014804.35824.da

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Abstract

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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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)
ORCID: Aiello, Robert J.
Brees, Dominique
Venue: Arteriosclerosis, Thrombosis, and Vascular Biology
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 2002-04
Volume: 22
Issue: 4
Pages: 630-637
ISSN: 1079-5642 (ISSN-L)
1524-4636
DOI: 10.1161/01.atv.0000014804.35824.da
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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Increased Atherosclerosis in Hyperlipidemic Mice With Inactivation of ABCA1 in Macrophages

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