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

Palmer, A.M., Murphy, N. and Graham, A. (2004) Triglyceride-rich lipoproteins inhibit cholesterol efflux to apolipoprotein (apo) A1 from human macrophage foam cells. Atherosclerosis, 173 (1). pp. 27-38. ISSN 0021-9150

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To link to this item DOI: 10.1016/j.atherosclerosis.2003.12.001

Abstract/Summary

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 (48h) 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 mug/ml, 0-24 h) inhibited the efflux of exogenously radiolabelled ([H-3]), endogenously synthesised ([C-14]) 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. (C) 2003 Elsevier Ireland Ltd. All rights reserved.

Item Type:Article
Refereed:Yes
Divisions:Faculty of Life Sciences > School of Chemistry, Food and Pharmacy > Department of Food and Nutritional Sciences
ID Code:13094
Uncontrolled Keywords:atherosclerosis, HDL, apolipoprotein A1, macrophage foam cells, cholesterol efflux, triglyceride-rich lipoproteins, HIGH-DENSITY-LIPOPROTEIN, HORMONE-SENSITIVE LIPASE, CASSETTE, TRANSPORTER 1, MONOCYTE-DERIVED MACROPHAGES, STEROL-DEPENDENT, REGULATION, CORONARY-ARTERY-DISEASE, HUMAN THP-1 MACROPHAGES, SCAVENGER, RECEPTOR-BI, TANGIER-DISEASE, CHYLOMICRON REMNANTS

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