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Triglyceride-rich lipoproteins inhibit cholesterol efflux to apolipoprotein (apo) A1 from human macrophage foam cells

  • Anna M Palmer
    Correspondence
    Corresponding author. Present address: Hugh Sinclair Unit of Human Nutrition, School of Food Biosciences, The University of Reading, P.O. Box 226, Reading RG6 6AP, UK. Tel.: +44-118-378-8727; fax: +44-118-931-8703.
    Affiliations
    Department of Biochemistry and Molecular Biology, Royal Free and University College Medical School, Royal Free Campus, Rowland Hill Street, London NW3 2PF, UK
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  • Nuala Murphy
    Affiliations
    Department of Biochemistry and Molecular Biology, Royal Free and University College Medical School, Royal Free Campus, Rowland Hill Street, London NW3 2PF, UK
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  • Annette Graham
    Affiliations
    Department of Biochemistry and Molecular Biology, Royal Free and University College Medical School, Royal Free Campus, Rowland Hill Street, London NW3 2PF, UK
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      Abstract

      High circulating levels of triglyceride-rich lipoproteins (TGRL) represent an independent risk factor for coronary artery disease. Here, we show that TGRL inhibit the efflux of cholesterol from ‘foam cell’ macrophages to lipid-poor apolipoprotein (apo) A1, and may thereby inhibit arterial reverse cholesterol transport and promote the formation of atherosclerotic lesions. Human (THP-1) monocyte-derived macrophages were pre-incubated (48 h) with acetylated low-density lipoprotein (AcLDL) to provide a foam cell model of cholesterol efflux to apoA1. Pre-incubation of macrophage ‘foam cells’ with TGRL (0–200 μg/ml, 0–24 h) inhibited the efflux of exogenously radiolabelled ([Math Eq]), endogenously synthesised ([Math Eq]) and cellular cholesterol mass to lipid-poor apoA1, but not control medium, during a (subsequent) efflux period. This inhibition is dependent upon the length of prior exposure to, and concentration of, TGRL employed, but is independent of changes in intracellular triglyceride accumulation or turnover of the cholesteryl ester pool. Despite the negative impact of TGRL on cholesterol efflux, major proteins involved in this process—namely apoE, ABCA1, SR-B1 and caveolin-1—were unaffected by TGRL pre-incubation, suggesting that exposure to these lipoproteins inhibits an alternate, and possibly novel, anti-atherogenic pathway.

      Abbreviations:

      ABC (ATP binding cassette), AcLDL (acetylated low-density lipoprotein), apo (apolipoprotein), BSA (bovine serum albumin), CAV-1 (caveolin-1), CE (cholesteryl ester), SR-B1 (scavenger receptor-B1), TG (triglyceride/triacylglycerol), TGRL (triglyceride-rich lipoproteins)

      Keywords

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