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Increased ABCA1 activity protects against atherosclerosis
Open accessAbstract
The ABC transporter ABCA1 plays a key role in the first steps of the reverse cholesterol transport pathway by mediating lipid efflux from macrophages. Previously, it was demonstrated that human ABCA1 overexpression in vivo in transgenic mice results in a mild elevation of plasma HDL levels and increased efflux of cholesterol from macrophages. In this study, we determined the effect of overexpression of ABCA1 on atherosclerosis development. Human ABCA1 transgenic mice (BAC(+)) were crossed with ApoE(-/-) mice, a strain that spontaneously develop atherosclerotic lesions. BAC(+)ApoE(-/-) mice developed dramatically smaller, less-complex lesions as compared with their ApoE(-/-) counterparts. In addition, there was increased efflux of cholesterol from macrophages isolated from the BAC(+)ApoE(-/-) mice. Although the increase in plasma HDL cholesterol levels was small, HDL particles from BAC(+)ApoE(-/-) mice were significantly better acceptors of cholesterol. Lipid analysis of HDL particles from BAC(+)ApoE(-/-) mice revealed an increase in phospholipid levels, which was correlated significantly with their ability to enhance cholesterol efflux.
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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 [12]
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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 [12]
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Metadata
- Authors
- Singaraja, R. R., Fievet, C., Castro, G., James, E. R., Hennuyer, N., Clee, S. M., Bissada, N., Choy, J. C., Fruchart, J.-C., McManus, B. M., Staels, B., & Hayden, M. R.
- Affiliations
- University of British Columbia (CA)
- Inserm (FR)
- Corresponding author
- Hayden, Michael R.
- ORCID
- Venue
- Journal of Clinical Investigation
- Published
- 2002-07-01
- Volume
- 110
- Issue
- 1
- Pages
- 35-42
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC151034
- OpenAlex
- W2097061706
- Cited by
- 250
- References
- 45
- Citations by year
- 2024: 2 · 2023: 1 · 2022: 5 · 2021: 8 · 2020: 5 · 2019: 3 · 2018: 3 · 2017: 6 · 2016: 11 · 2015: 9 · 2014: 9 · 2013: 10 · 2012: 8
- FWCI
- 22.28
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Canadian Institutes of Health Research
- 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 › Oncology › Drug Transport and Resistance Mechanisms
- Keywords
- ABCA1, atherosclerosis, reverse cholesterol transport, HDL cholesterol, macrophage cholesterol efflux, ApoE-deficient mice, transgenic mice, phospholipids, HDL particle composition, atherosclerotic plaque
- MeSH terms
- Animals, Apolipoproteins A, Apolipoproteins E, Arteriosclerosis, Biological Transport, Active, Cholesterol, Humans, Lipoproteins, HDL, Macrophages, Mice, Transgenic, Phospholipids, Tissue Distribution, Apolipoprotein A-I, Mice, Knockout, ATP-Binding Cassette Transporters, Mice, ATP Binding Cassette Transporter 1
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