ABCA1 Contributes to Macrophage Deposition of Extracellular Cholesterol

Overview

Journal J Lipid Res

Publisher Elsevier

Specialty Biochemistry

Date 2015 Jul 24

PMID 26203076

Citations 18

Authors

Xueting Jin

Sebastian R Freeman

Boris Vaisman

Ying Liu

Janet Chang

Neta Varsano

Lia Addadi

Alan Remaley

Howard S Kruth

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

An update on ox-LDL-inducing vascular smooth muscle cell-derived foam cells in atherosclerosis.

Guo J, Du L Front Cell Dev Biol. 2024; 12:1481505.

PMID: 39524227 PMC: 11543427. DOI: 10.3389/fcell.2024.1481505.

Navigating the Maze of Kinases: CaMK-like Family Protein Kinases and Their Role in Atherosclerosis.

Teuwen J, van der Vorst E, Maas S Int J Mol Sci. 2024; 25(11).

PMID: 38892400 PMC: 11172518. DOI: 10.3390/ijms25116213.

iPS-cell-derived microglia promote brain organoid maturation via cholesterol transfer.

Shin Park D, Kozaki T, Tiwari S, Moreira M, Khalilnezhad A, Torta F Nature. 2023; 623(7986):397-405.

PMID: 37914940 DOI: 10.1038/s41586-023-06713-1.

Foam Cells in Atherosclerosis: Novel Insights Into Its Origins, Consequences, and Molecular Mechanisms.

Gui Y, Zheng H, Cao R Front Cardiovasc Med. 2022; 9:845942.

PMID: 35498045 PMC: 9043520. DOI: 10.3389/fcvm.2022.845942.

Apolipoprotein M promotes cholesterol uptake and efflux from mouse macrophages.

Yao S, Zheng F, Yu Y, Zhan Y, Xu N, Luo G FEBS Open Bio. 2021; 11(6):1607-1620.

PMID: 33830664 PMC: 8167864. DOI: 10.1002/2211-5463.13157.

References

Tulenko T, Chen M, Mason P, Mason R . Physical effects of cholesterol on arterial smooth muscle membranes: evidence of immiscible cholesterol domains and alterations in bilayer width during atherogenesis. J Lipid Res. 1998; 39(5):947-56. View

Kessler N, Addadi L . Monoclonal antibodies that specifically recognize crystals of dinitrobenzene. FASEB J. 1996; 10(12):1435-42. DOI: 10.1096/fasebj.10.12.8903514. View

Kennedy M, Barrera G, Nakamura K, Baldan A, Tarr P, Fishbein M . ABCG1 has a critical role in mediating cholesterol efflux to HDL and preventing cellular lipid accumulation. Cell Metab. 2005; 1(2):121-31. DOI: 10.1016/j.cmet.2005.01.002. View

Vaughan A, Oram J . ABCG1 redistributes cell cholesterol to domains removable by high density lipoprotein but not by lipid-depleted apolipoproteins. J Biol Chem. 2005; 280(34):30150-7. DOI: 10.1074/jbc.M505368200. View

Duong P, Collins H, Nickel M, Lund-Katz S, Rothblat G, Phillips M . Characterization of nascent HDL particles and microparticles formed by ABCA1-mediated efflux of cellular lipids to apoA-I. J Lipid Res. 2006; 47(4):832-43. DOI: 10.1194/jlr.M500531-JLR200. View

Mulya A, Lee J, Gebre A, Thomas M, Colvin P, Parks J . Minimal lipidation of pre-beta HDL by ABCA1 results in reduced ability to interact with ABCA1. Arterioscler Thromb Vasc Biol. 2007; 27(8):1828-36. DOI: 10.1161/ATVBAHA.107.142455. View

Wang X, Collins H, Ranalletta M, Fuki I, Billheimer J, Rothblat G . Macrophage ABCA1 and ABCG1, but not SR-BI, promote macrophage reverse cholesterol transport in vivo. J Clin Invest. 2007; 117(8):2216-24. PMC: 1924499. DOI: 10.1172/JCI32057. View

Vedhachalam C, Duong P, Nickel M, Nguyen D, Dhanasekaran P, Saito H . Mechanism of ATP-binding cassette transporter A1-mediated cellular lipid efflux to apolipoprotein A-I and formation of high density lipoprotein particles. J Biol Chem. 2007; 282(34):25123-30. DOI: 10.1074/jbc.M704590200. View

Scheffer L, Futerman A, Addadi L . Antibody labeling of cholesterol/ceramide ordered domains in cell membranes. Chembiochem. 2007; 8(18):2286-94. DOI: 10.1002/cbic.200700482. View

10.

Marcel Y, Ouimet M, Wang M . Regulation of cholesterol efflux from macrophages. Curr Opin Lipidol. 2008; 19(5):455-61. DOI: 10.1097/MOL.0b013e32830f4a1d. View

11.

Sankaranarayanan S, Oram J, Asztalos B, Vaughan A, Lund-Katz S, Adorni M . Effects of acceptor composition and mechanism of ABCG1-mediated cellular free cholesterol efflux. J Lipid Res. 2008; 50(2):275-84. PMC: 2636919. DOI: 10.1194/jlr.M800362-JLR200. View

12.

Nandi S, Ma L, Denis M, Karwatsky J, Li Z, Jiang X . ABCA1-mediated cholesterol efflux generates microparticles in addition to HDL through processes governed by membrane rigidity. J Lipid Res. 2008; 50(3):456-466. DOI: 10.1194/jlr.M800345-JLR200. View

13.

Stefulj J, Panzenboeck U, Becker T, Hirschmugl B, Schweinzer C, Lang I . Human endothelial cells of the placental barrier efficiently deliver cholesterol to the fetal circulation via ABCA1 and ABCG1. Circ Res. 2009; 104(5):600-8. DOI: 10.1161/CIRCRESAHA.108.185066. View

14.

Larrede S, Quinn C, Jessup W, Frisdal E, Olivier M, Hsieh V . Stimulation of cholesterol efflux by LXR agonists in cholesterol-loaded human macrophages is ABCA1-dependent but ABCG1-independent. Arterioscler Thromb Vasc Biol. 2009; 29(11):1930-6. DOI: 10.1161/ATVBAHA.109.194548. View

15.

Ong D, Anzinger J, Leyva F, Rubin N, Addadi L, Kruth H . Extracellular cholesterol-rich microdomains generated by human macrophages and their potential function in reverse cholesterol transport. J Lipid Res. 2010; 51(8):2303-13. PMC: 2903806. DOI: 10.1194/jlr.M005660. View

16.

Marim F, Silveira T, Lima Jr D, Zamboni D . A method for generation of bone marrow-derived macrophages from cryopreserved mouse bone marrow cells. PLoS One. 2010; 5(12):e15263. PMC: 3003694. DOI: 10.1371/journal.pone.0015263. View

17.

Favari E, Zanotti I, Zimetti F, Ronda N, Bernini F, Rothblat G . Probucol inhibits ABCA1-mediated cellular lipid efflux. Arterioscler Thromb Vasc Biol. 2004; 24(12):2345-50. DOI: 10.1161/01.ATV.0000148706.15947.8a. View

18.

Rosenson R, Brewer Jr H, Davidson W, Fayad Z, Fuster V, Goldstein J . Cholesterol efflux and atheroprotection: advancing the concept of reverse cholesterol transport. Circulation. 2012; 125(15):1905-19. PMC: 4159082. DOI: 10.1161/CIRCULATIONAHA.111.066589. View

19.

Ziblat R, Fargion I, Leiserowitz L, Addadi L . Spontaneous formation of two-dimensional and three-dimensional cholesterol crystals in single hydrated lipid bilayers. Biophys J. 2012; 103(2):255-64. PMC: 3400773. DOI: 10.1016/j.bpj.2012.05.025. View

20.

Fisher E, Feig J, Hewing B, Hazen S, Smith J . High-density lipoprotein function, dysfunction, and reverse cholesterol transport. Arterioscler Thromb Vasc Biol. 2012; 32(12):2813-20. PMC: 3501261. DOI: 10.1161/ATVBAHA.112.300133. View