ATP-Binding Cassette Cholesterol Transporters and Cardiovascular Disease

Oram, John F.; Vaughan, Ashley M.

doi:10.1161/01.res.0000250171.54048.5c

Cited by 411Cholesterol and Lipid MetabolismLipoproteins and Cardiovascular HealthAtherosclerosis and Cardiovascular Diseases

ATP-Binding Cassette Cholesterol Transporters and Cardiovascular Disease

Oram, John F., Vaughan, Ashley M.·2006·Circulation Research

DOI 10.1161/01.res.0000250171.54048.5c

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Abstract

A hallmark of atherosclerotic cardiovascular disease (CVD) is the accumulation of cholesterol in arterial macrophages. Factors that modulate circulating and tissue cholesterol levels have major impacts on initiation, progression, and regression of CVD. Four members of the ATP-binding cassette (ABC) transporter family play important roles in this modulation. ABCA1 and ABCG1 export excess cellular cholesterol into the HDL pathway and reduce cholesterol accumulation in macrophages. ABCG5 and ABCG8 form heterodimers that limit absorption of dietary sterols in the intestine and promote cholesterol elimination from the body through hepatobiliary secretion. All 4 transporters are induced by the same sterol-sensing nuclear receptor system. ABCA1 expression and activity are also highly regulated posttranscriptionally by diverse processes. ABCA1 mutations can cause a severe HDL-deficiency syndrome characterized by cholesterol deposition in tissue macrophages and prevalent atherosclerosis. ABCG5 or ABCG8 mutations can cause sitosterolemia, in which patients accumulate cholesterol and plant sterols in the circulation and develop premature CVD. Disrupting Abca1 or Abcg1 in mice promotes accumulation of excess cholesterol in macrophages, and manipulating mouse macrophage ABCA1 expression affects atherogenesis. Overexpressing ABCG5 and ABCG8 in mice attenuates diet-induced atherosclerosis in association with reduced circulating and liver cholesterol. Metabolites elevated in individuals with the metabolic syndrome and diabetes destabilize ABCA1 protein and inhibit transcription of all 4 transporters. Thus, impaired ABC cholesterol transporters might contribute to the enhanced atherogenesis associated with common inflammatory and metabolic disorders. Their beneficial effects on cholesterol homeostasis have made these transporters important new therapeutic targets for preventing and reversing CVD.

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Since ABCA1 and ABCG1 work in tandem to facilitate cholesterol removal from the macrophages, the reduction in their expression would implicate a reduced potential of these monocyte-derived macrophages to egress cholesterol to HDL acceptors.
“Since ABCA1 and ABCG1 work in tandem to facilitate cholesterol removal from the macrophages54, the reduction in their expression would implicate a reduced potential of these monocyte-derived macrophages to egress cholesterol to HDL acceptors55.”
From Prolonged sleep restriction induces changes in pathways involved in cholesterol metabolism and inflammatory responses (2016) · cites this paper as [55]

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Reduction in ABCG1 in Type 2 Diabetic Mice Increases Macrophage Foam Cell Formation
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Authors: Oram, J. F., & Vaughan, A. M.
Affiliations: University of Washington (US)
ORCID: Vaughan, Ashley M.
Venue: Circulation Research
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 2006-11-10
Volume: 99
Issue: 10
Pages: 1031-1043
ISSN: 0009-7330 (ISSN-L)
1524-4571
DOI: 10.1161/01.res.0000250171.54048.5c
OpenAlex: W2129181154
Cited by: 411
References: 187
Citations by year: 2026: 3 · 2025: 10 · 2024: 8 · 2023: 16 · 2022: 13 · 2021: 16 · 2020: 11 · 2019: 12 · 2018: 13 · 2017: 11 · 2016: 26 · 2015: 19 · 2014: 25 · 2013: 21 · 2012: 31
FWCI: 6.13
Type: journal article
Language: en
Open access: closed
Locations: Circulation Research (publishedVersion)
PubMed (publishedVersion)
Funders: National Heart, Lung, and Blood Institute (HL-18645, HL-55362, R01HL075340, HL075340, P01HL018645, R01HL055362)
National Institute of Diabetes and Digestive and Kidney Diseases (DK 02456)
Topics: Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
Keywords: ABC transporters, ABCA1, ABCG1, ABCG5, ABCG8, atherosclerosis, cholesterol homeostasis, HDL cholesterol, macrophage cholesterol accumulation, sitosterolemia, post-transcriptional regulation, metabolic syndrome, diabetes mellitus, atherogenesis, therapeutic target
MeSH terms: Animals, Cholesterol, Homeostasis, Humans, Lipoproteins, HDL, ATP-Binding Cassette Transporters, Atherosclerosis

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ATP-Binding Cassette Cholesterol Transporters and Cardiovascular Disease

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