Combined deficiency of ABCA1 and ABCG1 promotes foam cell accumulation and accelerates atherosclerosis in mice
Open accessAbstract
HDLs protect against the development of atherosclerosis, but the underlying mechanisms are poorly understood. HDL and its apolipoproteins can promote cholesterol efflux from macrophage foam cells via the ATP-binding cassette transporters ABCA1 and ABCG1. Experiments addressing the individual roles of ABCA1 and ABCG1 in the development of atherosclerosis have produced mixed results, perhaps because of compensatory upregulation in the individual KO models. To clarify the role of transporter-mediated sterol efflux in this disease process, we transplanted BM from Abca1(-/-)Abcg1(-/-) mice into LDL receptor-deficient mice and administered a high-cholesterol diet. Compared with control and single-KO BM recipients, Abca1(-/-)Abcg1(-/-) BM recipients showed accelerated atherosclerosis and extensive infiltration of the myocardium and spleen with macrophage foam cells. In experiments with isolated macrophages, combined ABCA1 and ABCG1 deficiency resulted in impaired cholesterol efflux to HDL or apoA-1, profoundly decreased apoE secretion, and increased secretion of inflammatory cytokines and chemokines. In addition, these cells showed increased apoptosis when challenged with free cholesterol or oxidized LDL loading. These results suggest that the combined effects of ABCA1 and ABCG1 in mediating macrophage sterol efflux are central to the antiatherogenic properties of HDL.
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In reverse cholesterol transport, peripheral tissues export their excess cholesterol to HDL using the cholesterol export pumps ABCA1 and ABCG1.
“In a process termed reverse cholesterol transport, peripheral tissues export their excess cholesterol to HDL using the cholesterol export pumps ABCA1 and ABCG1 (44).”
From Expression of miR-33 from an SREBP2 Intron Inhibits Cholesterol Export and Fatty Acid Oxidation* (2010) · cites this paper as [44]
The Introduction (page not provided) describes HDL-mediated cholesterol removal from peripheral tissues and identifies ABCA1 and ABCG1 as cholesterol-efflux transporters. It distinguishes their acceptors, however: ABCA1 exports to lipid-poor apoA-1, not mature HDL particles, whereas ABCG1 exports to HDL. Thus the claim is too broad in saying both pumps export cholesterol to HDL. (LLM, conf=0.86)
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- Authors
- Yvan-Charvet, L., Ranalletta, M., Wang, N., Han, S., Terasaka, N., Li, R., Welch, C., & Tall, A. R.
- Affiliations
- Columbia University (US)
- Venue
- Journal of Clinical Investigation
- Published
- 2007-11-08
- Volume
- 117
- Issue
- 12
- Pages
- 3900-8
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC2066200
- OpenAlex
- W2170535838
- Cited by
- 536
- References
- 4
- Citations by year
- 2026: 10 · 2025: 10 · 2024: 12 · 2023: 28 · 2022: 30 · 2021: 31 · 2020: 29 · 2019: 29 · 2018: 34 · 2017: 20 · 2016: 28 · 2015: 28 · 2014: 31 · 2013: 41 · 2012: 40
- FWCI
- 31.28
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Philippe Foundation
- National Institutes of Health
- National Heart, Lung, and Blood Institute (P01HL054591, HL 54591)
- Topics
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Keywords
- ABCA1, ABCG1, atherosclerosis, HDL cholesterol, foam cells, cholesterol efflux, sterol efflux, apolipoprotein A-I, apoE secretion, macrophage apoptosis, oxidized LDL, inflammatory cytokines, chemokines, bone marrow transplantation, LDL receptor deficiency, high-cholesterol diet
- MeSH terms
- ATP Binding Cassette Transporter, Subfamily G, Member 1, Animals, Apolipoproteins E, Cholesterol, Foam Cells, Lipoproteins, Lipoproteins, HDL, Lipoproteins, LDL, Myocardium, Spleen, Apolipoprotein A-I, Mice, Knockout, ATP-Binding Cassette Transporters, Atherosclerosis, Mice, ATP Binding Cassette Transporter 1
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