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Publication : ABCA1 contributes to macrophage deposition of extracellular cholesterol.

First Author  Jin X Year  2015
Journal  J Lipid Res Volume  56
Issue  9 Pages  1720-6
PubMed ID  26203076 Mgi Jnum  J:329785
Mgi Id  MGI:6862963 Doi  10.1194/jlr.M060053
Citation  Jin X, et al. (2015) ABCA1 contributes to macrophage deposition of extracellular cholesterol. J Lipid Res 56(9):1720-6
abstractText  We previously reported that cholesterol-enriched macrophages excrete cholesterol into the extracellular matrix. A monoclonal antibody that detects cholesterol microdomains labels the deposited extracellular particles. Macro-phage deposition of extracellular cholesterol depends, in part, on ABCG1, and this cholesterol can be mobilized by HDL components of the reverse cholesterol transport process. The objective of the current study was to determine whether ABCA1 also contributes to macrophage deposition of extracellular cholesterol. ABCA1 functioned in extracellular cholesterol deposition. The liver X receptor agonist, TO901317 (TO9), an ABCA1-inducing factor, restored cholesterol deposition that was absent in cholesterol-enriched ABCG1(-/-) mouse macrophages. In addition, the ABCA1 inhibitor, probucol, blocked the increment in cholesterol deposited by TO9-treated wild-type macrophages, and completely inhibited deposition from TO9-treated ABCG1(-/-) macrophages. Lastly, ABCA1(-/-) macrophages deposited much less extracellular cholesterol than wild-type macrophages. These findings demonstrate a novel function of ABCA1 in contributing to macrophage export of cholesterol into the extracellular matrix.
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