Cited by 53Cholesterol and Lipid MetabolismLipoproteins and Cardiovascular HealthDrug Transport and Resistance Mechanisms

Enhancing apolipoprotein A-I-dependent cholesterol efflux elevates cholesterol export from macrophages in vivo

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Mukhamedova, Nigora, Escher, Genevieve, D'Souza, Wilissa, Tchoua, Urbain, Grant, Angela, Krozowski, Zigmund, Bukrinsky, Michael, Sviridov, Dmitri·2008·Journal of Lipid Research

Abstract

Eight proteins potentially involved in cholesterol efflux [ABCA1, ABCG1, CYP27A1, phospholipid transfer protein (PLTP), scavenger receptor type BI (SR-BI), caveolin-1, cholesteryl ester transfer protein, and apolipoprotein A-I (apoA-I)] were overexpressed alone or in combination in RAW 264.7 macrophages. When apoA-I was used as an acceptor, overexpression of the combination of ABCA1, CYP27A1, PLTP, and SR-BI (Combination I) enhanced the efflux by 4.3-fold. It was established that the stimulation of efflux was due to increased abundance of ABCA1 and increased apoA-I binding to non-ABCA1 sites on macrophages. This combination caused only a small increase of the efflux to isolated HDL. When HDL was used as an acceptor, overexpression of caveolin-1 or a combination of caveolin-1 and SR-BI (Combination II) was the most active, doubling the efflux to HDL, without affecting the efflux to apoA-I. When tested in the in vivo mouse model of cholesterol efflux, overexpression of ABCA1 and Combination I elevated cholesterol export from macrophages to plasma, liver, and feces, whereas overexpression of caveolin-1 or Combination II did not have an effect. We conclude that pathways of cholesterol efflux using apoA-I as an acceptor make a predominant contribution to cholesterol export from macrophages in vivo.

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Authors
Mukhamedova, N., Escher, G., D'Souza, W., Tchoua, U., Grant, A., Krozowski, Z., Bukrinsky, M., & Sviridov, D.
Affiliations
  • Baker Heart and Diabetes Institute (AU)
  • George Washington University (US)
Venue
Journal of Lipid Research
Publisher
Elsevier BV
Published
2008-11
Volume
49
Issue
11
Pages
2312-2322
ISSN
0022-2275 (ISSN-L)
OpenAlex
W2073185340
Cited by
53
References
44
Citations by year
2026: 1 · 2025: 2 · 2024: 1 · 2023: 2 · 2020: 3 · 2019: 5 · 2018: 2 · 2017: 8 · 2016: 2 · 2015: 1 · 2014: 1 · 2013: 6 · 2012: 6
FWCI
4.57
Type
journal article
Language
en
Open access
Locations
  • Journal of Lipid Research (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Fogarty International Center (R03TW006238)
  • National Institute of Diabetes and Digestive and Kidney Diseases (R21DK072926)
Topics
  • Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
  • Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
  • Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
Keywords
apolipoprotein A-I, cholesterol efflux, macrophages, ABCA1, caveolin-1, scavenger receptor class B type I, phospholipid transfer protein, CYP27A1, HDL cholesterol, atherosclerosis, cholesterol export
MeSH terms
Animals, Biological Transport, Active, Cell Line, Cholesterol, Lipoproteins, HDL, Macrophages, Signal Transduction, Apolipoprotein A-I, Mice

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