HDL, ABC transporters, and cholesterol efflux: implications for the treatment of atherosclerosis
Open accessAbstract
High-density lipoprotein (HDL) has been identified as a potential target in the treatment of atherosclerotic vascular disease. The failure of torcetrapib, an inhibitor of cholesteryl ester transfer protein (CETP) that markedly increased HDL levels in a clinical trial, has called into doubt the efficacy of HDL elevation. Recent analysis suggests that failure may have been caused by off-target toxicity and that HDL is functional and promotes regression of atherosclerosis. New studies highlight the central importance of the ATP-binding cassette (ABC) transporters ABCA1 and ABCG1 in reducing macrophage foam cell formation, inflammation, and atherosclerosis. A variety of approaches to increasing HDL may eventually be successful in treating atherosclerosis.
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The primary function of ABCA1 and ABCG1 is efflux of cholesterol onto poorly-lipidated ApoA1 and HDL particles respectively.
“Since the primary function of ABCA1 and ABCG1 is the efflux of cholesterol onto poorly-lipidated ApoA1 and HDL particles respectively (Tall et al., 2008)”
From Genetic dissection of the impact of miR-33a and miR-33b during the progression of atherosclerosis (2017) · cites this paper as Tall et al., 2008
ABCA1 acts as a cellular cholesterol export pump and has the unique capability to export cholesterol to lipid-free apoAI, involved in HDL particle formation and reverse cholesterol transport.
“ABCA1 acts as a cellular cholesterol export pump.Although there are a number of cholesterol efflux pumps, ABCA1 has the unique capability to export cholesterol to lipid-free apolipoprotein AI (apoAI) and is therefore involved in the initial step of high-density lipoprotein particle formation in liver, as well as reverse cholesterol transport (26).”
From Expression of miR-33 from an SREBP2 Intron Inhibits Cholesterol Export and Fatty Acid Oxidation* (2010) · cites this paper as [26]
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BackgroundInfluentialCholesterol efflux protein, ABCA1, supports anticancer functions of myeloid immune cells
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- Authors
- Tall, A. R., Yvan-Charvet, L., Terasaka, N., Pagler, T., & Wang, N.
- Affiliations
- Columbia University Irving Medical Center (US)
- Corresponding author
- Wang, Nan
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2008-05
- Volume
- 7
- Issue
- 5
- Pages
- 365-375
- ISSN
- 1550-4131 (ISSN-L)
- OpenAlex
- W2006921001
- Cited by
- 540
- References
- 6
- Citations by year
- 2026: 10 · 2025: 11 · 2024: 17 · 2023: 31 · 2022: 18 · 2021: 33 · 2020: 26 · 2019: 21 · 2018: 31 · 2017: 31 · 2016: 29 · 2015: 29 · 2014: 31 · 2013: 42 · 2012: 46
- FWCI
- 7.58
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (P01HL054591)
- 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
- high-density lipoprotein, atherosclerosis, cholesterol efflux, ABCA1, ABCG1, ABC transporters, cholesteryl ester transfer protein, torcetrapib, HDL-targeted therapy, foam cells, inflammation, off-target toxicity
- MeSH terms
- Animals, Cholesterol, Humans, Lipoproteins, HDL, ATP-Binding Cassette Transporters, Atherosclerosis
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