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Cited by 284Cholesterol and Lipid MetabolismAtherosclerosis and Cardiovascular DiseasesLipoproteins and Cardiovascular Health

The Macrophage Cholesterol Exporter ABCA1 Functions as an Anti-inflammatory Receptor

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Tang, Chongren, Liu, Yuhua, Kessler, Peter S., Vaughan, Ashley M., Oram, John F.·2009·Journal of Biological Chemistry
DOI 10.1074/jbc.m109.047472PMC PMC2781648
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Abstract

ATP-binding cassette transporter A1 (ABCA1) is a cell membrane protein that exports excess cholesterol from cells to apolipoprotein (apo) A-I, the major protein in high density lipoproteins. Genetic studies have shown that ABCA1 protects against cardiovascular disease. The interaction of apoA-I with ABCA1 promotes cholesterol removal and activates signaling molecules, such as Janus kinase 2 (JAK2), that optimize the lipid export activity of ABCA1. Here we show that the ABCA1-mediated activation of JAK2 also activates STAT3, which is independent of the lipid transport function of ABCA1. ABCA1 contains two candidate STAT3 docking sites that are required for the apoA-I/ABCA1/JAK2 activation of STAT3. The interaction of apoA-I with ABCA1-expressing macrophages suppressed the ability of lysopolysaccaride to induce the inflammatory cytokines interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha, which was reversed by silencing STAT3 or ABCA1. Thus, the apoA-I/ABCA1 pathway in macrophages functions as an anti-inflammatory receptor through activation of JAK2/STAT3. These findings implicate ABCA1 as a direct molecular link between the cardioprotective effects of cholesterol export from arterial macrophages and suppressed inflammation.

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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 central in the antiatherogenic mechanism.

    “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 <sup>−/−</sup> Mice (2012) · cites this paper as [15]

    The Introduction says ABCA1 exports cholesterol from cells to apoA-I, and the Discussion links ABCA1-mediated cholesterol export to cardioprotection in atherosclerotic lesions. Our copy does not establish the claim about ABCG1-mediated efflux to apoA-I, so the citation supports only the ABCA1 part. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • ABCA1 acts directly as an anti-inflammatory receptor independent of its lipid transport activities.

    “Moreover, ABCA1 has been reported to act directly as an anti-inflammatory receptor independent of its lipid transport activities.15”

    From MicroRNA‐33 Deficiency Reduces the Progression of Atherosclerotic Plaque in ApoE <sup>−/−</sup> Mice (2012) · cites this paper as [15]

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Authors
Tang, C., Liu, Y., Kessler, P. S., Vaughan, A. M., & Oram, J. F.
Affiliations
University of Washington (US)
Corresponding author
Oram, John F.
ORCID
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2009-11
Volume
284
Issue
47
Pages
32336-32343
ISSN
0021-9258 (ISSN-L)
DOI
10.1074/jbc.m109.047472
PMC
PMC2781648
OpenAlex
W2033102824
Cited by
284
References
4
Citations by year
2026: 3 · 2025: 18 · 2024: 12 · 2023: 17 · 2022: 17 · 2021: 25 · 2020: 11 · 2019: 10 · 2018: 19 · 2017: 10 · 2016: 10 · 2015: 23 · 2014: 18 · 2013: 21 · 2012: 18
FWCI
23.66
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Heart, Lung, and Blood Institute (P01HL092969, HL-085437, R01HL085437, R01HL055362)
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
ABCA1, apolipoprotein A-I, STAT3, JAK2, macrophages, anti-inflammatory signaling, cholesterol export, high-density lipoprotein, inflammatory cytokines, cardiovascular disease
MeSH terms
Animals, Anti-Inflammatory Agents, Cholesterol, Cricetinae, Humans, Lipids, Macrophages, Mice, Inbred C57BL, Tumor Necrosis Factor-alpha, Signal Transduction, Interleukin-6, ATP-Binding Cassette Transporters, Gene Silencing, STAT3 Transcription Factor, Mice, Interleukin-1beta, ATP Binding Cassette Transporter 1

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