Regulation of cholesterol efflux from macrophages

Current Opinion in Lipidology

Volumn 19, Issue 5, 2008, Pages 455-461

  Marcel, Yves L ^a,b   Ouimet, Mireille ^a   Wang, Ming Dong ^a  

^a UNIVERSITY OF OTTAWA HEART INSTITUTE   (Canada)

^b NONE   (Canada)

Author keywords

Atherosclerosis; ATP binding cassette transporter A1; ATP binding cassette transporter G1; Reverse cholesterol transport

Indexed keywords

ABC TRANSPORTER A1; ABC TRANSPORTER G1; APOLIPOPROTEIN A1; CHOLESTEROL; CHOLESTEROL ESTER; FAT DROPLET; HIGH DENSITY LIPOPROTEIN;

ATHEROSCLEROSIS; CELL MIGRATION; CELL SURFACE; CHOLESTEROL TRANSPORT; ENDOCYTOSIS; MACROPHAGE; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; REVIEW; TRANSCRIPTION REGULATION;

ANIMALS; ATHEROSCLEROSIS; ATP-BINDING CASSETTE TRANSPORTERS; BIOLOGICAL TRANSPORT; CHOLESTEROL; HUMANS; MACROPHAGES;

EID: 53649101824     PISSN: 09579672     EISSN: None     Source Type: Journal    
DOI: 10.1097/MOL.0b013e32830f4a1d     Document Type: Review

References (89)

1. Burgess JW, Frank PG, Franklin V, et al. Deletion of the C-terminal domain of apolipoprotein A-l impairs cell surface binding and lipid efflux in macrophage. Biochemistry 1999; 38:14524-14533.
2. Vedhachalam C, Ghering AB, Davidson WS, et al. ABCAI-induced cell surface binding sites for ApoA-l. Arterioscler Thromb Vasc Biol 2007; 27:1603-1609. The first demonstration that apoA-l associates with two cell surface binding sites, one low capacity involving direct ABCA1 interaction, the other high capacity created by ABCA1 activity and involving interaction with lipids.
3. **], the authors formulate a threestep model for apoA-l interaction with ABCA1 and the formation of nascent lipidated apoA-l particles.
4. Denis M, Haidar B, Marcil M, et al. Characterization of oligomeric human ATP binding cassette transporter A1. Potential implications for determining the structure of nascent high density lipoprotein particles. J Biol Chem 2004; 279:41529-41536.
5. Silva RA, Hilliard GM, Fang J, et al. A three-dimensional molecular model of lipid-free apolipoprotein A-l determined by cross-linking/mass spectrometry and sequence threading. Biochemistry 2005; 44:2759-2769.
6. Zhu HL, Atkinson D. Conformation and lipid binding of a C-terminal (198-243) peptide of human apolipoprotein A-l. Biochemistry 2007; 46:1624-1634.
7. Mulya A, Lee JY, Gebre AK, et al. Minimal lipidation of prebeta HDL by ABCA1 results in reduced ability to interact with ABCA1. Arterioscler Thromb Vasc Biol 2007; 27:1828-1836. In cells that express ABCA1 and no other contributor to HDL formation and maturation only preβ-HDL are formed, which when isolated are unable to react further with ABCA1. This provides evidence for the contribution of other transporters for a HDL formation.
8. Neufeld EB, Remaley AT, Demosky SJ, et al. Cellular localization and trafficking of the human ABCA1 transporter. J Biol Chem 2001; 276:27584-27590.
9. Neufeld EB, Stonik JA, Demosky SJ Jr, et al. The ABCA1 transporter modulates late endocytic trafficking: insights from the correction of the genetic defect in Tangier disease. J Biol Chem 2004; 279:15571-15578.
10. *].
11. Faulkner LE, Panagotopulos SE, Johnson JD, et al. An analysis of the role of a retroendocytosis pathway in ATP-binding cassette transporter (ABCA1)-mediated cholesterol efflux from macrophages. J Lipid Res 2008; 49:1322-1332. A very careful analysis of endocytosis contribution to ABCA1-dependent efflux is based on specific apoA-llabeling, short-term pulse-chase analysis and inhibitors of endocytosis and concludes that endocytosis contributes mostly to apoA-l degradation.
12. Denis M, Landry YD, Zha X. ATP-binding cassette A1-mediated lipidation of apolipoprotein A-l occurs at the plasma membrane and not in the endocytic compartments. J Biol Chem 2008; 283:16178-16186. Florescence microscopy of apoA-l and ABCA1 and analysis of released apoA-l led to the conclusion that endocytosis leads to degradation more than to lipidation.
13. Krimbou L, Hajj HH, Blain S, et al. Biogenesis and speciation of nascent apoA-lcontaining particles in various cell lines. J Lipid Res 2005; 46:1668-1677.
14. Duong PT, Collins HL, Nickel M, et al. Characterization of nascent HDL particles and microparticles formed by ABCA1-mediated efflux of cellular lipids to apoA-l. J Lipid Res 2006; 47:832-843.
15. Chau P, Nakamura Y, Fielding CJ, Fielding PE Mechanism of prebeta-HDL formation and activation. Biochemistry 2006; 45:3981-3987.
16. Cserepes J, Szentpetery Z, Seres L, et al. Functional expression and characterization of the human ABCG1 and ABCG4 proteins: indications for heterodimerization. Biochem Biophys Res Commun 2004; 320:860-867.
17. Wang N, Lan D, Chen W, et al. ATP-binding cassette transporters G1 and G4 mediate cellular cholesterol efflux to high-density lipoproteins. Proc Natl Acad Sci U S A 2004; 101:9774-9779.
18. Vaughan AM, Oram JF. ABCA1 and ABCG1 or ABCG4 act sequentially to remove cellular cholesterol and generate cholesterol-rich HDL. J Lipid Res 2006; 47:2433-2443.
19. Gelissen IC, Harris M, Rye KA, et al. ABCA1 and ABCG1 synergize to mediate cholesterol export to apoA-l. Arterioscler Thromb Vasc Biol 2006; 26:534-540.
20. Lorenzi I, Von Eckardstein A, Radosavljevic S, Rohrer L. Lipidation of apolipoprotein A-l by ATP-binding cassette transporter (ABC) A1 generates an interaction partner for ABCG1 but not for scavenger receptor B1. Biochim Biophys Acta 2008; 1781:306-313.
21. Wang MD, Kiss RS, Franklin V, et al. Different cellular traffic of LDL-cholesterol and acetylated LDL-cholesterol leads to distinct reverse cholesterol transport pathways. J Lipid Res 2007; 48:633-645.
22. Kennedy MA, Barrera GC, Nakamura K, et al. ABCG1 has a critical role in mediating cholesterol efflux to HDL and preventing cellular lipid accumulation. Cell Metab 2005; 1:121-131.
23. Cavelier C, Lorenzi I, Rohrer L, Von Eckardstein A. Lipid efflux by the ATP-binding cassette transporters ABCA1 and ABCG1. Biochim Biophys Acta 2006; 1761:655-666.
24. Jessup W, Gelissen IC, Gaus K, Kritharides L. Roles of ATP binding cassette transporters A1 and G1, scavenger receptor Bl and membrane lipid domains in cholesterol export from macrophages. Curr Opin Lipidol 2006; 17:247-257.
25. Adomi MP, Zimetti F, Billheimer JT, et al. The roles of different pathways in the release of cholesterol from macrophages. J Lipid Res 2007; 48:2453-2462.
26. **] to demonstrate the in-vivo contribution of ABCA1 to reverse cholesterol transport from macrophages.
27. Wang X, Collins HL Ranalletta M, et al. Macrophage ABCA1 and ABCG1, but not SR-BI, promote macrophage reverse cholesterol transport in vivo. J Clin Invest 2007; 117:2216-2224. An important study showing that ABCG1 contributes to reverse cholesterol transport in vivo in a manner additive to ABCA1.
28. Yu L, Cao G, Repa J, Stangl H. Sterol regulation of scavenger receptor class B type I in macrophages. J Lipid Res 2004; 45:889-899.
29. Zhang W, Yancey PG, Su YR, et al. Inactivation of macrophage scavenger receptor class B type I promotes atherosclerotic lesion development in apolipoprotein E-deficient mice. Circulation 2003; 108:2268-2263.
30. Calpe-Berdiel L, Rotllan N, Palomer X, et al. Direct evidence in vivo of impaired macrophage-specific reverse cholesterol transport in ATP-binding cassette transporter A1-deficient mice. Biochim Biophys Acta 2005; 1738:6-9.
31. Ranalletta M, Wang N, Han S, et al. Decreased atherosclerosis in low-density lipoprotein receptor knockout mice transplanted with Abcg1 -/- bone marrow. Arterioscler Thromb Vasc Biol 2006; 26:2308-2315.
32. Baldan A, Pei L, Lee R, Tarr P, et al. Impaired development of atherosclerosis in hyperlipidemic Ldlr-/- and ApoE-/- mice transplanted with Abcg1 -/- bone marrow. Arterioscler Thromb Vasc Biol 2006; 26:2301-2307.
33. Out R, Hoekstra M, Hildebrand RB, et al. Macrophage ABCG1 deletion disrupts lipid homeostasis in alveolar macrophages and moderately influences atherosclerotic lesion development in LDL receptor-deficient mice. Arterioscler Thromb Vasc Biol 2006; 26:2295-2300.
34. Out R, Hoekstra M, Meurs I, et al. Total body ABCG1 expression protects against early atherosclerotic lesion development in mice. Arterioscler Thromb Vasc Biol 2007; 27:594-599.
35. Yvan-Charvet L, Ranalletta M, Wang N, et al. Combined deficiency of ABCA1 and ABCG1 promotes foam cell accumulation and accelerates atherosclerosis in mice. J Clin Invest 2007; 117:3900-3908. A complex phenotype is described for the bone marrow transplantation of ABCA1-/-/ABCG1 -/- macrophage in LDLr-/- mice, which develop increased lesions related to increased macrophage inflammation and increased apoptosis.
36. Out R, Hoekstra M, Habets K, et al. Combined deletion of macrophage ABCA1 and ABCG1 leads to massive lipid accumulation in tissue macrophages and distinct atherosclerosis at relatively low plasma cholesterol levels. Arterioscler Thromb Vasc Biol 2008; 28:258-264. A surprisingly powerful hypocholesterolemic effect of bone marrow transplantation with ABCA1 -/-/ABCG1 -/- macrophages normalize plasma cholesterol and decrease lesion size in LDLr-/- mice.
37. Out R, Jessup W, Le Goff W, et al. Coexistence of foam cells and hypocholesterolemia in mice lacking the ABC transporters A1 and G1. Circ Res 2008; 102:113-120.
38. Mauldin JP, Nagelin MH, Wojcik AJ, et al. Reduced expression of ATP-binding cassette transporter G1 increases cholesterol accumulation in macrophages of patients with type 2 diabetes mellitus. Circulation 2008; 117:2785-2792. An original and potentially very significant study demonstrates a downregulation of ABCG1 in diabetic mice macrophages, which readily develop foam cell phenotypes. This suggests that regulation of ABCG1 could have a protective role in diabetic atherosclerosis.
39. Chen W, Sun Y, Welch C, et al. Preferential ATP-binding cassette transporter A1-mediated cholesterol efflux from late endosomes/lysosomes. J Biol Chem 2001; 276:43564-43569.
40. Chen W, Wang N, Tall AR. A PEST deletion mutant of ABCA1 shows impaired intemalization and defective cholesterol efflux from late endosomes. J Biol Chem 2005; 280:29277-29281.
41. Brown MS, Goldstein JL. A receptor-mediated pathway for cholesterol homeostasis. Science 1986; 232:34-47.
42. Zhang JR, Coleman T, Langmade SJ, et al. Niemann-Pick C1 protects against atherosclerosis in mice via regulation of macrophage intracellular cholesterol trafficking. J Clin Invest 2008; 118:2281-2290.
43. Welch CL, Sun Y, Arey BJ, et al. Spontaneous atherothrombosis and medial degradation in Apoe-/-, Npc1-/- mice. Circulation 2007; 116:2444-2452.
44. Martin S, Driessen K, Nixon SJ, et al. Regulated localization of Rab18 to lipid droplets: effects of lipdytic stimulation and inhibition of lipid droplet catabolism. J Biol Chem 2005; 280:42325-42335.
45. Ozeki S, Cheng J, Tauchi-Sato K, et al. Rab18 localizes to lipid droplets and induces their close apposition to the endoplasmic reticulum-derived membrane. J Cell Sci 2005; 118:2601-2611.
46. Ouimet M, Wang MD, Cadotte N, et al. Epoxycholesterol impairs cholesteryl ester hydrolysis in macrophage foam cells, resulting in decreased cholesterol efflux Arterioscler Thromb Vasc Biol 2008; 28:1144-1150. A potent natural LXR ligand decreases cholesterol efflux in cholesterol-loaded, but not in cholesterol-unloaded macrophages. This study demonstrates that cholesteryl ester hydrolysis in lipid droplet is limiting for cholesterol efflux in macrophage foam cells, and that LXR agonists with LXR-independent cellular effects in foam cells are to be avoided for regression of atherosclerosis.
47. Dolinsky VW, Gilham D, Alam M, et al. Triacylglycerol hydrolase: role in intracellular lipid metabolism. Cell Mol Life Sci 2004; 61:1633-1651.
48. Ghosh S. Cholesteryl ester hydrolase in human monocyte/macrophage: cloning, sequencing, and expression of full-length cDNA. Physiol Genomics 2000; 2:1-8.
49. Zhao B, Natarajan R, Ghosh S. Human liver cholesteryl ester hydrolase: cloning, molecular characterization, and role in cellular cholesterol homeostasis. Physiol Genomics 2005; 23:304-310.
50. Zhao B, Song J, St Clair R, Ghosh S. Stable over-expression of human macrophage cholesteryl ester hydrolase (CEH) results in enhanced free cholesterol efflux from human THP1-macrophages. Am J Physiol Cell Physiol 2007; 292:C405-C412.
51. Zhao B, Song J, Chow WN, et al. Macrophage-specific transgenic expression of cholesteryl ester hydrolase significantly reduces atherosclerosis and lesion necrosis in Ldlr mice. J Clin Invest 2007; 117:2983-2992. The study provides direct evidence that enhancing cholesteryl ester hydrolysis in macrophages in vivo is antiatherogenic, and highlights the benefits of potentially manipulating this pathway to promote RCT.
52. Yeaman SJ. Hormone-sensitive lipase: new roles for an old enzyme. Biochem J 2004; 379:11-22.
53. Choy HA, Wang XP, Schotz MC. Reduced atherosclerosis in hormone-sensitive lipase transgenic mice overexpressing cholesterol acceptors. Biochim Biophys Acta 2003; 1634:76-85.
54. Zha X, Genest J Jr, McPherson R. Endocytosis is enhanced in Tangier fibroblasts: possible role of ATP-binding cassette protein A1 in endosomal vesicular transport. J Biol Chem 2001; 276:39476-39483.
55. Landry YD, Denis M, Nandi S, et al. ATP-binding cassette transporter A1 expression disrupts raft membrane microdomains through its ATPase-related functions. J Biol Chem 2006; 281:36091-36101.
56. Zha X, Gauthier A, Genest J, McPherson R. Secretory vesicular transport from the Golgi is altered during ATP-binding cassette protein A1 (ABCA1)-mediated cholesterol efflux. J Biol Chem 2003; 278:10002-10005.
57. Ors⊙ E, Broccardo C, Kaminski WE, et al. Transport of lipids from Golgi to plasma membrane is defective in Tangier disease patients and Abc1-deficient mice. Nat Genet 2000; 24:192-196.
58. Schmitz G, Langmann T. Transcriptional regulatory networks in lipid metabolism control ABCA1 expression. Biochim Biophys Acta 2005; 1735:1-19.
59. Thymiakou E, Zannis VI, Kardassis D. Physical and functional interactions between liver X receptor/retinoid X receptor and Sp1 modulate the transcriptional induction of the human ATP binding cassette transporter A1 gene by oxysterols and retinoids. Biochemistry 2007; 46:11473-11483.
60. Witzlack T, Wenzeck T, Thiery J, Orth M. cAMP-induced expression of ABCA1 is associated with MAP-kinase-pathway activation. Biochem Biophys Res Commun 2007; 363:89-94.
61. Wang MD, Franklin V, Sundaram M, et al. Differential Regulation of ATP binding cassette protein A1 Expression and ApoA-l lipidation by Niemann-Pick type C1 in murine hepatocytes and macrophages. J Biol Chem 2007; 282:22525-22533. Demonstration of a cell-specific regulation of ABCA1.
62. bull;] show that oxysterol-binding proteins might be responsible for this difference.
63. bull;].
64. Singaraja RR, James ER, Crim J, et al. Alternate transcripts expressed in response to diet reflect tissue-specific regulation of ABCA1. J Lipid Res 2005; 46:2061-2071.
65. Pullinger CR, Hakamata H, Duchateau PN, et al. Analysis of hABC1 gene 5′ end: additional peptide sequence, promoter region, and four polymorphisms. Biochem Biophys Res Commun 2000; 271:451-455.
66. Tamehiro N, Shigemoto-Mogami Y, Kakeya T, et al. Sterol regulatory element-binding protein-2- and liver X receptor-driven dual promoter regulation of hepatic ABC transporter A1 gene expression: mechanism underlying the unique response to cellular cholesterol status. J Biol Chem 2007; 282:21090-21099. The first mechanistic demonstration of the regulation of ABCA1 mRNA expression in a tissue-specific manner.
67. Iwamoto N, Abe-Dohmae S, Ayaori M, et al. ATP-binding cassette transporter A1 gene transcription is downregulated by activator protein 2alpha. Doxazosin inhibits activator protein 2alpha and increases high-density lipoprotein biogenesis independent of alpha1-adrenoceptor blockade. Circ Res 2007; 101:156-165.
68. Oram JF, Lawn RM, Garvin MR, Wade DP. ABCA1 is the cAMP-inducible apolipoprotein receptor that mediates cholesterol secretion from macrophages. J Biol Chem 2000; 275:34508-34511.
69. Wang Y, Oram JF. Unsaturated fatty acids inhibit cholesterol efflux from macrophages by increasing degradation of ATP-binding cassette transporter A1. J Biol Chem 2002; 277:5692-5697.
70. Wang N, Chen W, Linsel-Nitschke P, et al. A PEST sequence in ABCA1 regulates degradation by calpain protease and stabilization of ABCA1 by apoA-l. J Clin Invest 2003; 111:99-107.
71. Arakawa R, Yokoyama S. Helical apolipoproteins stabilize ATP-binding cassette transporter A1 by protecting it from thiol protease-mediated degradation. J Biol Chem 2002; 277:22426-22429.
72. Feng B, Tabas I. ABCA1-mediated cholesterol efflux is defective in free cholesterol-loaded macrophages. Mechanism involves enhanced ABCA1 degradation in a process requiring full NPC1 activity. J Biol Chem 2002; 277:43271-43280.
73. Haidar B, Kiss RS, Sarov-Blat L, et al. Cathepsin D, a lysosomal protease, regulates ABCA1-mediated lipid efflux. J Biol Chem 2006; 281:39971-39981.
74. Bowden K, Ridgway ND. Oxysterol binding protein (OSBP) negatively regulates ATP binding cassette transporter A1 (ABCA1) protein stability. J Biol Chem 2008; 283:18210-18217.
75. Tang C, Vaughan AM, Oram JF. Janus kinase 2 modulates the apolipoprotein interactions with ABCA1 required for removing cellular cholesterol. J Biol Chem 2004; 279:7622-7628.
76. Martinez L, Agerholm-Larsen B, Wang N, et al. Phosporylation of a pest sequence in ABCA1 promotes calpain degradation and is reversed by APOA-I. J Biol Chem 2003; 278:37368-37374.
77. Ito J, Nagayasu Y, Ueno S, Yokoyama S, Apolipoprotein-mediated cellular lipid release requires replenishment of sphingomyeiin in a phosphatidylcholinespecific phospholipase C-dependent manner. J Biol Chem 2002; 277: 44709-44714.
78. Yamauchi Y, Hayashi M, Abe-Dohmae S, Yokoyama S. ApoA-l activates PKCalpha signaling to phosphorylate and stabilize ABCA1 for the HDL assembly. J Biol Chem 2003; 278:47890-47897.
79. Kiss RS, Maric J, Marcel YL. Lipid efflux in human and mouse macrophagic cells: evidence for differential regulation of phospholipid and cholesterol efflux. J Lipid Res 2005; 46:1877-1887.
80. Wang Y, Oram JF. Unsaturated fatty acids phosphorylate and destabilize ABCA1 through a phospholipase D2 pathway. J Biol Chem 2005; 280:35896-35903.
81. Wang Y, Oram JF. Unsaturated fatty acids phosphorylate and destabilize ABCA1 through a protein kinase C delta pathway. J Lipid Res 2007; 48: 1062-1068. A further mechanistic study from Oram's laboratory showing that unsaturated fatty acids destabilize the ABCA1 protein via PKC pathway.
82. Haidar B, Denis M, Marcil M, et al. Apolipoprotein Al activates cellular cAMP signaling through the ABCA1 transporter. J Biol Chem 2004; 279:9963-9969.
83. See RH, Caday-Malcolm RA, Singaraja RR, et al. Protein kinase A site-specific phosphorylation regulates ATP-binding cassette A1 (ABCA1)-mediated phospholipid efflux. J Biol Chem 2002; 277:41835-41842.
84. Roosbeek S, Peelman F, Verhee A, et al. Phosphorylation by protein kinase CK2 modulates the activity of the ATP binding cassette A1 transporter. J Biol Chem 2004; 279:37779-37788.
85. Buechler C, Boettcher A, Bared SM, et al. The carboxyterminus of the ATP-binding cassette transporter A1 interacts with a beta2-syntrophin/ utrophin complex. Biochem Biophys Res Commun 2002; 293:759-765.
86. Okuhira K, Fitzgerald ML, Sarracino DA, et al. Purification of ATP-binding cassette transporter A1 and associated binding proteins reveals the importance of beta1-syntrophin in cholesterol efflux. J Biol Chem 2005; 280:39653-39664.
87. Munehira Y, Ohnishi T, Kawamoto S, et al. Alpha1-syntrophin modulates turnover of ABCA1. J Biol Chem 2004; 279:15091-15095.
88. Ahn AH, Freener CA, Gussoni E, et al. The three human syntrophin genes are expressed in diverse tissues, have distinct chromosomal locations, and each bind to dystrophin and its relatives. J Biol Chem 1996; 271:2724-2730.
89. Tamehiro N, Zhou S, Okuhira K, et al. SPTLC1 binds ABCA1 to negatively regulate trafficking and cholesterol efflux activity of the transporter. Biochemistry 2008; 47:6138-6147. An extension study of [87] in Fitzgerald's laboratory. Both investigations showed that ABCA1 adaptor-proteins regulate ABCA1 protein stability at the cell surface.