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Role of apoA-I, ABCA1, LCAT, and SR-BI in the biogenesis of HDL

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Abstract

The concentration, composition, shape, and size of plasma high-density lipoprotein (HDL) are determined by numerous proteins that influence its biogenesis, remodeling, and catabolism. The discoveries of the HDL receptor (scavenger receptor class B type I, SR-BI) and the ABCA1 (ATP-binding cassette transporter A1) lipid transporter provided two missing links that were necessary to understand the biogenesis and some of the functions of HDL. Existing data indicate that functional interactions between apoA-I and ABCA1 are necessary for the initial lipidation of apoA-I. Through a series of intermediate steps, lipidated apoA-I proceeds to form discoidal HDL particles that can be converted to spherical particles by the action of lecithin:cholesterol acyltransferase (LCAT). Discoidal and spherical HDL can interact functionally with SR-BI and these interactions lead to selective lipid uptake and net efflux of cholesterol and thus remodel HDL. Defective apoA-I/ABCA1 interactions prevent lipidation of apoA-I that is necessary for the formation of HDL particles. In the same way, specific mutations in apoA-I or LCAT prevent the conversion of discoidal to spherical HDL particles. The interactions of lipid-bound apoA-I with SR-BI are affected in vitro by specific mutations in apoA-I or SR-BI. Furthermore, deficiency of SR-BI affects the lipid and apolipoprotein composition of HDL and is associated with increased susceptibility to atherosclerosis. Here we review the current status of the pathway of HDL biogenesis and mutations in apoA-I, ABCA1, and SR-BI that disrupt different steps of the pathway and may lead to dyslipidemia and atherosclerosis in mouse models. The phenotypes generated in experimental mouse models for apoA-I, ABCA1, LCAT, SR-BI, and other proteins of the HDL pathway may facilitate early diagnosis of similar phenotypes in the human population and provide guidance for proper treatment.

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Abbreviations

Apo:

Apolipoprotein

ABC:

ATP-binding cassette transporter

ApoA-I−/− mice:

ApoA-I-deficient mice

BLT4:

Block lipid transfer 4

CETP:

Cholesteryl ester transfer protein

EL:

Endothelial lipase

EM:

Electron microscopy

FC:

Free cholesterol

FPLC:

Fast pressure liquid chromatography

HDL:

High density lipoprotein

HL:

Hepatic lipase

IDL:

Intermediate density lipoprotein

LCAT:

Lecithin:cholesterol acyltransferase

LDL:

Low density lipoprotein

LDLr:

LDL receptor

LpL:

Lipoprotein lipase

PL:

Phospholipids

PLTP:

Phospholipid transfer protein

SR-BI:

Scavenger receptor class B type I

VLDL:

Very low density lipoprotein

WT:

Wild-type

References

  1. Zannis VI, Chroni A, Kypreos KE, Kan HY, Cesar TB, Zanni EE, Kardassis D (2004) Probing the pathways of chylomicron and HDL metabolism using adenovirus-mediated gene transfer. Curr Opin Lipidol 15:151–166

    Article  PubMed  CAS  Google Scholar 

  2. Krieger M (2001) Scavenger receptor class B type I is a multiligand HDL receptor that influences diverse physiologic systems. J Clin Invest 108:793–797

    Article  PubMed  CAS  Google Scholar 

  3. Wang N, Lan D, Chen W, Matsuura F, Tall AR (2004) ATP-binding cassette transporters G1 and G4 mediate cellular cholesterol efflux to high-density lipoproteins. Proc Natl Acad Sci U S A 101:9774–9779

    Article  PubMed  CAS  Google Scholar 

  4. Zannis VI, Cole FS, Jackson CL, Kurnit DM, Karathanasis SK (1985) Distribution of apolipoprotein A-I, C-II, C-III, and E mRNA in fetal human tissues. Time-dependent induction of apolipoprotein E mRNA by cultures of human monocyte-macrophages. Biochemistry 24:4450–4455

    Article  PubMed  CAS  Google Scholar 

  5. Matsunaga T, Hiasa Y, Yanagi H, Maeda T, Hattori N, Yamakawa K, Yamanouchi Y, Tanaka I, Obara T, Hamaguchi H (1991) Apolipoprotein A-I deficiency due to a codon 84 nonsense mutation of the apolipoprotein A-I gene. Proc Natl Acad Sci U S A 88:2793–2797

    PubMed  CAS  Google Scholar 

  6. Williamson R, Lee D, Hagaman J, Maeda N (1992) Marked reduction of high density lipoprotein cholesterol in mice genetically modified to lack apolipoprotein A-I. Proc Natl Acad Sci U S A 89:7134–7138

    PubMed  CAS  Google Scholar 

  7. Li WH, Tanimura M, Luo CC, Datta S, Chan L (1988) The apolipoprotein multigene family: biosynthesis, structure, structure–function relationships, and evolution. J Lipid Res 29:245–271

    PubMed  CAS  Google Scholar 

  8. Nolte RT, Atkinson D (1992) Conformational analysis of apolipoprotein A-I and E-3 based on primary sequence and circular dichroism. Biophys J 63:1221–1239

    PubMed  CAS  Google Scholar 

  9. Borhani DW, Rogers DP, Engler JA, Brouillette CG (1997) Crystal structure of truncated human apolipoprotein A-I suggests a lipid-bound conformation. Proc Natl Acad Sci U S A 94:12291–12296

    Article  PubMed  CAS  Google Scholar 

  10. Borhani DW, Engler JA, Brouillette CG (1999) Crystallization of truncated human apolipoprotein A-I in a novel conformation. Acta Crystallogr D Biol Crystallogr 55(Pt 9):1578–1583

    Article  PubMed  CAS  Google Scholar 

  11. Segrest JP, Jones MK, De Loof H, Brouillette CG, Venkatachalapathi YV, Anantharamaiah GM (1992) The amphipathic helix in the exchangeable apolipoproteins: a review of secondary structure and function. J Lipid Res 33:141–166

    PubMed  CAS  Google Scholar 

  12. Segrest JP, Jones MK, Klon AE, Sheldahl CJ, Hellinger M, De Loof H, Harvey SC (1999) A detailed molecular belt model for apolipoprotein A-I in discoidal high density lipoprotein. J Biol Chem 274:31755–31758

    Article  PubMed  CAS  Google Scholar 

  13. Segrest JP (1977) Amphipathic helixes and plasma lipoproteins: thermodynamic and geometric considerations. Chem Phys Lipids 18:7–22

    Article  PubMed  CAS  Google Scholar 

  14. Segrest JP, Li L, Anantharamaiah GM, Harvey SC, Liadaki KN, Zannis V (2000) Structure and function of apolipoprotein A-I and high-density lipoprotein. Curr Opin Lipidol 11:105–115

    Article  PubMed  CAS  Google Scholar 

  15. Panagotopulos SE, Horace EM, Maiorano JN, Davidson WS (2001) Apolipoprotein A-I adopts a belt-like orientation in reconstituted high density lipoproteins. J Biol Chem 276:42965–42970

    Article  PubMed  CAS  Google Scholar 

  16. Marcel YL, Kiss RS (2003) Structure–function relationships of apolipoprotein A-I: a flexible protein with dynamic lipid associations. Curr Opin Lipidol 14:151–157

    Article  PubMed  CAS  Google Scholar 

  17. Phillips JC, Wriggers W, Li Z, Jonas A, Schulten K (1997) Predicting the structure of apolipoprotein A-I in reconstituted high-density lipoprotein disks. Biophys J 73:2337–2346

    PubMed  CAS  Google Scholar 

  18. Sorci-Thomas MG, Thomas MJ (2002) The effects of altered apolipoprotein A-I structure on plasma HDL concentration. Trends Cardiovasc Med 12:121–128

    Article  PubMed  CAS  Google Scholar 

  19. Zannis VI, Kardassis D, Zanni EE (1993) Genetic mutations affecting human lipoproteins, their receptors, and their enzymes. Adv Hum Genet 21:145–319

    PubMed  CAS  Google Scholar 

  20. Yamakawa-Kobayashi K, Yanagi H, Fukayama H, Hirano C, Shimakura Y, Yamamoto N, Arinami T, Tsuchiya S, Hamaguchi H (1999) Frequent occurrence of hypoalphalipoproteinemia due to mutant apolipoprotein A-I gene in the population: a population-based survey. Hum Mol Genet 8:331–336

    Article  PubMed  CAS  Google Scholar 

  21. von Eckardstein A, Walter M, Holz H, Benninghoven A, Assmann G (1991) Site-specific methionine sulfoxide formation is the structural basis of chromatographic heterogeneity of apolipoproteins A-I, C-II, and C-III. J Lipid Res 32:1465–1476

    PubMed  Google Scholar 

  22. Panzenbock U, Stocker R (2005) Formation of methionine sulfoxide-containing specific forms of oxidized high-density lipoproteins. Biochim Biophys Acta 1703:171–181

    PubMed  Google Scholar 

  23. Shao B, Bergt C, Fu X, Green P, Voss JC, Oda MN, Oram JF, Heinecke JW (2005) Tyrosine 192 in apolipoprotein A-I is the major site of nitration and chlorination by myeloperoxidase, but only chlorination markedly impairs ABCA1-dependent cholesterol transport. J Biol Chem 280:5983–5993

    Article  PubMed  CAS  Google Scholar 

  24. Langmann T, Klucken J, Reil M, Liebisch G, Luciani MF, Chimini G, Kaminski WE, Schmitz G (1999) Molecular cloning of the human ATP-binding cassette transporter 1 (hABC1): evidence for sterol-dependent regulation in macrophages. Biochem Biophys Res Commun 257:29–33

    Article  PubMed  CAS  Google Scholar 

  25. Kielar D, Dietmaier W, Langmann T, Aslanidis C, Probst M, Naruszewicz M, Schmitz G (2001) Rapid quantification of human ABCA1 mRNA in various cell types and tissues by real-time reverse transcription-PCR. Clin Chem 47:2089–2097

    PubMed  CAS  Google Scholar 

  26. Neufeld EB, Demosky SJ Jr, Stonik JA, Combs C, Remaley AT, Duverger N, Santamarina-Fojo S, Brewer HB Jr (2002) The ABCA1 transporter functions on the basolateral surface of hepatocytes. Biochem Biophys Res Commun 297:974–979

    Article  PubMed  CAS  Google Scholar 

  27. Oram JF, Vaughan AM (2000) ABCA1-mediated transport of cellular cholesterol and phospholipids to HDL apolipoproteins. Curr Opin Lipidol 11:253–260

    Article  PubMed  CAS  Google Scholar 

  28. Wang N, Silver DL, Costet P, Tall AR (2000) Specific binding of ApoA-I, enhanced cholesterol efflux, and altered plasma membrane morphology in cells expressing ABC1. J Biol Chem 275:33053–33058

    Article  PubMed  CAS  Google Scholar 

  29. Remaley AT, Stonik JA, Demosky SJ, Neufeld EB, Bocharov AV, Vishnyakova TG, Eggerman TL, Patterson AP, Duverger NJ, Santamarina-Fojo S, Brewer HB Jr (2001) Apolipoprotein specificity for lipid efflux by the human ABCAI transporter. Biochem Biophys Res Commun 280:818–823

    Article  PubMed  CAS  Google Scholar 

  30. Francis GA, Knopp RH, Oram JF (1995) Defective removal of cellular cholesterol and phospholipids by apolipoprotein A-I in Tangier disease. J Clin Invest 96:78–87

    PubMed  CAS  Google Scholar 

  31. Bodzioch M, Orso E, Klucken J, Langmann T, Bottcher A, Diederich W, Drobnik W, Barlage S, Buchler C, Porsch-Ozcurumez M, Kaminski WE, Hahmann HW, Oette K, Rothe G, Aslanidis C, Lackner KJ, Schmitz G (1999) The gene encoding ATP-binding cassette transporter 1 is mutated in Tangier disease. Nat Genet 22:347–351

    Article  PubMed  CAS  Google Scholar 

  32. Rust S, Rosier M, Funke H, Real J, Amoura Z, Piette JC, Deleuze JF, Brewer HB, Duverger N, Denefle P, Assmann G (1999) Tangier disease is caused by mutations in the gene encoding ATP-binding cassette transporter 1. Nat Genet 22:352–355

    Article  PubMed  CAS  Google Scholar 

  33. Brooks-Wilson A, Marcil M, Clee SM, Zhang LH, Roomp K, van Dam M, Yu L, Brewer C, Collins JA, Molhuizen HO, Loubser O, Ouelette BF, Fichter K, Ashbourne-Excoffon KJ, Sensen CW, Scherer S, Mott S, Denis M, Martindale D, Frohlich J, Morgan K, Koop B, Pimstone S, Kastelein JJ, Hayden MR (1999) Mutations in ABC1 in Tangier disease and familial high-density lipoprotein deficiency. Nat Genet 22:336–345

    Article  PubMed  CAS  Google Scholar 

  34. Lawn RM, Wade DP, Garvin MR, Wang X, Schwartz K, Porter JG, Seilhamer JJ, Vaughan AM, Oram JF (1999) The Tangier disease gene product ABC1 controls the cellular apolipoprotein-mediated lipid removal pathway. J Clin Invest 104:R25–R31

    PubMed  CAS  Google Scholar 

  35. Marcil M, Brooks-Wilson A, Clee SM, Roomp K, Zhang LH, Yu L, Collins JA, van Dam M, Molhuizen HO, Loubster O, Ouellette BF, Sensen CW, Fichter K, Mott S, Denis M, Boucher B, Pimstone S, Genest J Jr, Kastelein JJ, Hayden MR (1999) Mutations in the ABC1 gene in familial HDL deficiency with defective cholesterol efflux. Lancet 354:1341–1346

    Article  PubMed  CAS  Google Scholar 

  36. Remaley AT, Schumacher UK, Stonik JA, Farsi BD, Nazih H, Brewer HB Jr (1997) Decreased reverse cholesterol transport from Tangier disease fibroblasts. Acceptor specificity and effect of brefeldin on lipid efflux. Arterioscler Thromb Vasc Biol 17:1813–1821

    PubMed  CAS  Google Scholar 

  37. Rogler G, Trumbach B, Klima B, Lackner KJ, Schmitz G (1995) HDL-mediated efflux of intracellular cholesterol is impaired in fibroblasts from Tangier disease patients. Arterioscler Thromb Vasc Biol 15:683–690

    PubMed  CAS  Google Scholar 

  38. Walter M, Gerdes U, Seedorf U, Assmann G (1994) The high density lipoprotein- and apolipoprotein A-I-induced mobilization of cellular cholesterol is impaired in fibroblasts from Tangier disease subjects. Biochem Biophys Res Commun 205:850–856

    Article  PubMed  CAS  Google Scholar 

  39. Orso E, Broccardo C, Kaminski WE, Bottcher A, Liebisch G, Drobnik W, Gotz A, Chambenoit O, Diederich W, Langmann T, Spruss T, Luciani MF, Rothe G, Lackner KJ, Chimini G, Schmitz G (2000) Transport of lipids from Golgi to plasma membrane is defective in tangier disease patients and Abc1-deficient mice. Nat Genet 24:192–196

    Article  PubMed  CAS  Google Scholar 

  40. Assmann G, von Eckardstein A, Brewer HB (2001) Familial analphalipoproteinemia: tangier disease. In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The metabolic and molecular basis of inherited disease. McGraw-Hill, New York, pp 2937–2960

    Google Scholar 

  41. McNeish J, Aiello RJ, Guyot D, Turi T, Gabel C, Aldinger C, Hoppe KL, Roach ML, Royer LJ, de Wet J, Broccardo C, Chimini G, Francone OL (2000) High density lipoprotein deficiency and foam cell accumulation in mice with targeted disruption of ATP-binding cassette transporter-1. Proc Natl Acad Sci U S A 97:4245–4250

    Article  PubMed  CAS  Google Scholar 

  42. Christiansen-Weber TA, Voland JR, Wu Y, Ngo K, Roland BL, Nguyen S, Peterson PA, Fung-Leung WP (2000) Functional loss of ABCA1 in mice causes severe placental malformation, aberrant lipid distribution, and kidney glomerulonephritis as well as high-density lipoprotein cholesterol deficiency. Am J Pathol 157:1017–1029

    PubMed  CAS  Google Scholar 

  43. Cohen JC, Kiss RS, Pertsemlidis A, Marcel YL, McPherson R, Hobbs HH (2004) Multiple rare alleles contribute to low plasma levels of HDL cholesterol. Science 305:869–872

    Article  PubMed  CAS  Google Scholar 

  44. Frikke-Schmidt R, Nordestgaard BG, Jensen GB, Tybjaerg-Hansen A (2004) Genetic variation in ABC transporter A1 contributes to HDL cholesterol in the general population. J Clin Invest 114:1343–1353

    Article  PubMed  CAS  Google Scholar 

  45. Timmins JM, Lee JY, Boudyguina E, Kluckman KD, Brunham LR, Mulya A, Gebre AK, Coutinho JM, Colvin PL, Smith TL, Hayden MR, Maeda N, Parks JS (2005) Targeted inactivation of hepatic Abca1 causes profound hypoalphalipoproteinemia and kidney hypercatabolism of apoA-I. J Clin Invest 115:1333–1342

    Article  PubMed  CAS  Google Scholar 

  46. Schmitz G, Robenek H, Lohmann U, Assmann G (1985) Interaction of high density lipoproteins with cholesteryl ester-laden macrophages: biochemical and morphological characterization of cell surface receptor binding, endocytosis and resecretion of high density lipoproteins by macrophages. EMBO J 4:613–622

    PubMed  CAS  Google Scholar 

  47. Schmitz G, Assmann G, Robenek H, Brennhausen B (1985) Tangier disease: a disorder of intracellular membrane traffic. Proc Natl Acad Sci U S A 82:6305–6309

    PubMed  CAS  Google Scholar 

  48. Neufeld EB, Stonik JA, Demosky SJ Jr, Knapper CL, Combs CA, Cooney A, Comly M, Dwyer N, Blanchette-Mackie J, Remaley AT, Santamarina-Fojo S, Brewer HB Jr (2004) The ABCA1 transporter modulates late endocytic trafficking: insights from the correction of the genetic defect in Tangier disease. J Biol Chem 279:15571–15578

    Article  PubMed  CAS  Google Scholar 

  49. von Eckardstein A, Langer C, Engel T, Schaukal I, Cignarella A, Reinhardt J, Lorkowski S, Li Z, Zhou X, Cullen P, Assmann G (2001) ATP binding cassette transporter ABCA1 modulates the secretion of apolipoprotein E from human monocyte-derived macrophages. FASEB J 15:1555–1561

    Article  PubMed  Google Scholar 

  50. Fitzgerald ML, Okuhira K, Short GF III, Manning JJ, Bell SA, Freeman MW (2004) ATP-binding cassette transporter A1 contains a novel C-terminal VFVNFA motif that is required for its cholesterol efflux and ApoA-I binding activities. J Biol Chem 279:48477–48485

    Article  PubMed  CAS  Google Scholar 

  51. Munehira Y, Ohnishi T, Kawamoto S, Furuya A, Shitara K, Imamura M, Yokota T, Takeda S, Amachi T, Matsuo M, Kioka N, Ueda K (2004) Alpha1-syntrophin modulates turnover of ABCA1. J Biol Chem 279:15091–15095

    Article  PubMed  CAS  Google Scholar 

  52. Buechler C, Boettcher A, Bared SM, Probst MC, Schmitz G (2002) The carboxyterminus of the ATP-binding cassette transporter A1 interacts with a beta2-syntrophin/utrophin complex. Biochem Biophys Res Commun 293:759–765

    Article  PubMed  CAS  Google Scholar 

  53. Bared SM, Buechler C, Boettcher A, Dayoub R, Sigruener A, Grandl M, Rudolph C, Dada A, Schmitz G (2004) Association of ABCA1 with syntaxin 13 and flotillin-1 and enhanced phagocytosis in tangier cells. Mol Biol Cell 15:5399–5407

    Article  PubMed  CAS  Google Scholar 

  54. Arakawa R, Hayashi M, Remaley AT, Brewer BH, Yamauchi Y, Yokoyama S (2004) Phosphorylation and stabilization of ATP binding cassette transporter A1 by synthetic amphiphilic helical peptides. J Biol Chem 279:6217–6220

    Article  PubMed  CAS  Google Scholar 

  55. Yamauchi Y, Hayashi M, Abe-Dohmae S, Yokoyama S (2003) Apolipoprotein A-I activates protein kinase C alpha signaling to phosphorylate and stabilize ATP binding cassette transporter A1 for the high density lipoprotein assembly. J Biol Chem 278:47890–47897

    Article  PubMed  CAS  Google Scholar 

  56. Roosbeek S, Peelman F, Verhee A, Labeur C, Caster H, Lensink MF, Cirulli C, Grooten J, Cochet C, Vandekerckhove J, Amoresano A, Chimini G, Tavernier J, Rosseneu M (2004) Phosphorylation by protein kinase CK2 modulates the activity of the ATP binding cassette A1 transporter. J Biol Chem 279:37779–37788

    Article  PubMed  CAS  Google Scholar 

  57. Martinez LO, Agerholm-Larsen B, Wang N, Chen W, Tall AR (2003) Phosphorylation of a pest sequence in ABCA1 promotes calpain degradation and is reversed by ApoA-I. J Biol Chem 278:37368–37374

    Article  PubMed  CAS  Google Scholar 

  58. Feng B, Tabas I (2002) 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 277:43271–43280

    Article  PubMed  CAS  Google Scholar 

  59. Wang Y, Oram JF (2002) Unsaturated fatty acids inhibit cholesterol efflux from macrophages by increasing degradation of ATP-binding cassette transporter A1. J Biol Chem 277:5692–5697

    Article  PubMed  CAS  Google Scholar 

  60. Joyce CW, Amar MJ, Lambert G, Vaisman BL, Paigen B, Najib-Fruchart J, Hoyt RF Jr, Neufeld ED, Remaley AT, Fredrickson DS, Brewer HB Jr, Santamarina-Fojo S (2002) The ATP binding cassette transporter A1 (ABCA1) modulates the development of aortic atherosclerosis in C57BL/6 and apoE-knockout mice. Proc Natl Acad Sci U S A 99:407–412

    Article  PubMed  CAS  Google Scholar 

  61. Attie AD, Kastelein JP, Hayden MR (2001) Pivotal role of ABCA1 in reverse cholesterol transport influencing HDL levels and susceptibility to atherosclerosis. J Lipid Res 42:1717–1726

    PubMed  CAS  Google Scholar 

  62. Aiello RJ, Brees D, Bourassa PA, Royer L, Lindsey S, Coskran T, Haghpassand M, Francone OL (2002) Increased atherosclerosis in hyperlipidemic mice with inactivation of ABCA1 in macrophages. Arterioscler Thromb Vasc Biol 22:630–637

    Article  PubMed  CAS  Google Scholar 

  63. Van Eck M, Bos IS, Kaminski WE, Orso E, Rothe G, Twisk J, Bottcher A, Van Amersfoort ES, Christiansen-Weber TA, Fung-Leung WP, van Berkel TJ, Schmitz G (2002) Leukocyte ABCA1 controls susceptibility to atherosclerosis and macrophage recruitment into tissues. Proc Natl Acad Sci U S A 99:6298–6303

    Article  PubMed  CAS  Google Scholar 

  64. Singaraja RR, Fievet C, Castro G, James ER, Hennuyer N, Clee SM, Bissada N, Choy JC, Fruchart JC, McManus BM, Staels B, Hayden MR (2002) Increased ABCA1 activity protects against atherosclerosis. J Clin Invest 110:35–42

    Article  PubMed  CAS  Google Scholar 

  65. Groen AK, Bloks VW, Bandsma RH, Ottenhoff R, Chimini G, Kuipers F (2001) Hepatobiliary cholesterol transport is not impaired in Abca1-null mice lacking HDL. J Clin Invest 108:843–850

    Article  PubMed  CAS  Google Scholar 

  66. Vaisman BL, Lambert G, Amar M, Joyce C, Ito T, Shamburek RD, Cain WJ, Fruchart-Najib J, Neufeld ED, Remaley AT, Brewer HB Jr, Santamarina-Fojo S (2001) ABCA1 overexpression leads to hyperalphalipoproteinemia and increased biliary cholesterol excretion in transgenic mice. J Clin Invest 108:303–309

    Article  PubMed  CAS  Google Scholar 

  67. Chambenoit O, Hamon Y, Marguet D, Rigneault H, Rosseneu M, Chimini G (2001) Specific docking of apolipoprotein A-I at the cell surface requires a functional ABCA1 transporter. J Biol Chem 276:9955–9960

    Article  PubMed  CAS  Google Scholar 

  68. Rigot V, Hamon Y, Chambenoit O, Alibert M, Duverger N, Chimini G (2002) Distinct sites on ABCA1 control distinct steps required for cellular release of phospholipids. J Lipid Res 43:2077–2086

    Article  PubMed  CAS  Google Scholar 

  69. Vaughan AM, Oram JF (2003) ABCA1 redistributes membrane cholesterol independent of apolipoprotein interactions. J Lipid Res 44:1373–1380

    Article  PubMed  CAS  Google Scholar 

  70. Panagotopulos SE, Witting SR, Horace EM, Hui DY, Maiorano JN, Davidson WS (2002) The role of apolipoprotein A-I helix 10 in apolipoprotein-mediated cholesterol efflux via the ATP-binding cassette transporter ABCA1. J Biol Chem 277:39477–39484

    Article  PubMed  CAS  Google Scholar 

  71. Fitzgerald ML, Morris AL, Rhee JS, Andersson LP, Mendez AJ, Freeman MW (2002) Naturally occurring mutations in the largest extracellular loops of ABCA1 can disrupt its direct interaction with apolipoprotein A-I. J Biol Chem 277:33178–33187

    Article  PubMed  CAS  Google Scholar 

  72. Chroni A, Liu T, Gorshkova I, Kan HY, Uehara Y, von Eckardstein A, Zannis VI (2003) The central helices of apoA-I can promote ATP-binding cassette transporter A1 (ABCA1)-mediated lipid efflux. Amino acid residues 220–231 of the wild-type apoA-I are required for lipid efflux in vitro and high density lipoprotein formation in vivo. J Biol Chem 278:6719–6730

    Article  PubMed  CAS  Google Scholar 

  73. Chroni A, Liu T, Fitzgerald ML, Freeman MW, Zannis VI (2004) Cross-linking and lipid efflux properties of apoA-I mutants suggest direct association between apoA-I helices and ABCA1. Biochemistry 43:2126–2139

    Article  PubMed  CAS  Google Scholar 

  74. Chroni A, Kan HY, Kypreos KE, Gorshkova IN, Shkodrani A, Zannis VI (2004) Substitutions of glutamate 110 and 111 in the middle helix 4 of human apolipoprotein A-I (apoA-I) by alanine affect the structure and in vitro functions of apoA-I and induce severe hypertriglyceridemia in apoA-I-deficient mice. Biochemistry 43:10442–10457

    Article  PubMed  CAS  Google Scholar 

  75. Natarajan P, Forte TM, Chu B, Phillips MC, Oram JF, Bielicki JK (2004) Identification of an apolipoprotein A-I structural element that mediates cellular cholesterol efflux and stabilizes ATP binding cassette transporter A1. J Biol Chem 279:24044–24052

    Article  PubMed  CAS  Google Scholar 

  76. Remaley AT, Thomas F, Stonik JA, Demosky SJ, Bark SE, Neufeld EB, Bocharov AV, Vishnyakova TG, Patterson AP, Eggerman TL, Santamarina-Fojo S, Brewer HB (2003) Synthetic amphipathic helical peptide mediated efflux of lipid from cells by an ABCA1-dependent and an ABCA1-independent pathway. J Lipid Res 44:828–836

    Article  PubMed  CAS  Google Scholar 

  77. Fitzgerald ML, Morris AL, Chroni A, Mendez AJ, Zannis VI, Freeman MW (2004) ABCA1 and amphipathic apolipoproteins form high-affinity molecular complexes required for cholesterol efflux. J Lipid Res 45:287–294

    Article  PubMed  CAS  Google Scholar 

  78. Nieland TJ, Chroni A, Fitzgerald ML, Maliga Z, Zannis VI, Kirchhausen T, Krieger M (2004) Cross-inhibition of SR-BI- and ABCA1-mediated cholesterol transport by the small molecules BLT-4 and glyburide. J Lipid Res 45:1256–1265

    Article  PubMed  CAS  Google Scholar 

  79. Reardon CA, Kan HY, Cabana V, Blachowicz L, Lukens JR, Wu Q, Liadaki K, Getz GS, Zannis VI (2001) In vivo studies of HDL assembly and metabolism using adenovirus-mediated transfer of ApoA-I mutants in ApoA-I-deficient mice. Biochemistry 40:13670–13680

    Article  PubMed  CAS  Google Scholar 

  80. Lapicka-Bodzioch K, Bodzioch M, Krull M, Kielar D, Probst M, Kiec B, Andrikovics H, Bottcher A, Hubacek J, Aslanidis C, Suttorp N, Schmitz G (2001) Homogeneous assay based on 52 primer sets to scan for mutations of the ABCA1 gene and its application in genetic analysis of a new patient with familial high-density lipoprotein deficiency syndrome. Biochim Biophys Acta 1537:42–48

    PubMed  CAS  Google Scholar 

  81. Stonik JA, Remaley AT, Demosky SJ, Neufeld EB, Bocharov A, Brewer HB (2004) Serum amyloid A promotes ABCA1-dependent and ABCA1-independent lipid efflux from cells. Biochem Biophys Res Commun 321:936–941

    Article  PubMed  CAS  Google Scholar 

  82. Francone OL, Subbaiah PV, van Tol A, Royer L, Haghpassand M (2003) Abnormal phospholipid composition impairs HDL biogenesis and maturation in mice lacking Abca1. Biochemistry 42:8569–8578

    Article  PubMed  CAS  Google Scholar 

  83. Fielding CJ, Fielding PE (1995) Molecular physiology of reverse cholesterol transport. J Lipid Res 36:211–228

    PubMed  CAS  Google Scholar 

  84. Lusa S, Jauhiainen M, Metso J, Somerharju P, Ehnholm C (1996) The mechanism of human plasma phospholipid transfer protein-induced enlargement of high-density lipoprotein particles: evidence for particle fusion. Biochem J 313(Pt 1):275–282

    PubMed  CAS  Google Scholar 

  85. Liang HQ, Rye KA, Barter PJ (1994) Dissociation of lipid free apolipoprotein A I from high density lipoproteins. J Lipid Res 35:1187–1199

    PubMed  CAS  Google Scholar 

  86. Xu N, Dahlback B (1999) A novel human apolipoprotein (apoM). J Biol Chem 274:31286–31290

    Article  PubMed  CAS  Google Scholar 

  87. Wolfrum C, Poy MN, Stoffel M (2005) Apolipoprotein M is required for prebeta-HDL formation and cholesterol efflux to HDL and protects against atherosclerosis. Nat Med 11:418–422

    Article  PubMed  CAS  Google Scholar 

  88. McLean J, Fielding C, Drayna D, Dieplinger H, Baer B, Kohr W, Henzel W, Lawn R (1986) Cloning and expression of human lecithin-cholesterol acyltransferase cDNA. Proc Natl Acad Sci U S A 83:2335–2339

    PubMed  CAS  Google Scholar 

  89. Fielding CJ, Shore VG, Fielding PE (1972) A protein cofactor of lecithin:cholesterol acyltransferase. Biochem Biophys Res Commun 46:1493–1498

    Article  PubMed  CAS  Google Scholar 

  90. Gordon DJ, Rifkind BM (1989) High-density lipoprotein—the clinical implications of recent studies. N Engl J Med 321:1311–1316

    Article  PubMed  CAS  Google Scholar 

  91. Santamarina-Fojo S, Hoeg JM, Assmann G, Brewer HB Jr (2001) Lecithin cholesterol acyltransferase deficiency and fish eye disease. In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The metabolic & molecular bases of inherited disease. McGraw-Hill, New York, pp 2817–2834

    Google Scholar 

  92. McManus DC, Scott BR, Frank PG, Franklin V, Schultz JR, Marcel YL (2000) Distinct central amphipathic alpha-helices in apolipoprotein A-I contribute to the in vivo maturation of high density lipoprotein by either activating lecithin-cholesterol acyltransferase or binding lipids. J Biol Chem 275:5043–5051

    Article  PubMed  CAS  Google Scholar 

  93. Scott BR, McManus DC, Franklin V, McKenzie AG, Neville T, Sparks DL, Marcel YL (2001) The N-terminal globular domain and the first class A amphipathic helix of apolipoprotein A-I are important for lecithin:cholesterol acyltransferase activation and the maturation of high density lipoprotein in vivo. J Biol Chem 276:48716–48724

    Article  PubMed  CAS  Google Scholar 

  94. Chroni A, Kan HY, Shkodrani A, Liu T, Zannis VI (2005) Deletions of helices 2 and 3 of human apoA-I are associated with severe dyslipidemia following adenovirus-mediated gene transfer in apoA-I-deficient mice. Biochemistry 44:4108–4117

    Article  PubMed  CAS  Google Scholar 

  95. Chroni A, Duka A, Kan HY, Liu T, Zannis VI (2005) Point mutations in apolipoprotein a-I mimic the phenotype observed in patients with classical lecithin:cholesterol acyltransferase deficiency. Biochemistry 44:14353–14366

    Article  PubMed  CAS  Google Scholar 

  96. Salinelli S, Lo JY, Mims MP, Zsigmond E, Smith LC, Chan L (1996) Structure–function relationship of lipoprotein lipase-mediated enhancement of very low density lipoprotein binding and catabolism by the low density lipoprotein receptor. Functional importance of a properly folded surface loop covering the catalytic center. J Biol Chem 271:21906–21913

    Article  PubMed  CAS  Google Scholar 

  97. Medh JD, Bowen SL, Fry GL, Ruben S, Andracki M, Inoue I, Lalouel JM, Strickland DK, Chappell DA (1996) Lipoprotein lipase binds to low density lipoprotein receptors and induces receptor-mediated catabolism of very low density lipoproteins in vitro. J Biol Chem 271:17073–17080

    Article  PubMed  CAS  Google Scholar 

  98. Pussinen PJ, Jauhiainen M, Metso J, Pyle LE, Marcel YL, Fidge NH, Ehnholm C (1998) Binding of phospholipid transfer protein (PLTP) to apolipoproteins A-I and A-II: location of a PLTP binding domain in the amino terminal region of apoA-I. J Lipid Res 39:152–161

    PubMed  CAS  Google Scholar 

  99. Jauhiainen M, Metso J, Pahlman R, Blomqvist S, van Tol A, Ehnholm C (1993) Human plasma phospholipid transfer protein causes high density lipoprotein conversion. J Biol Chem 268:4032–4036

    PubMed  CAS  Google Scholar 

  100. Tu AY, Nishida HI, Nishida T (1993) High density lipoprotein conversion mediated by human plasma phospholipid transfer protein. J Biol Chem 268:23098–23105

    PubMed  CAS  Google Scholar 

  101. von Eckardstein A, Jauhiainen M, Huang Y, Metso J, Langer C, Pussinen P, Wu S, Ehnholm C, Assmann G (1996) Phospholipid transfer protein mediated conversion of high density lipoproteins generates pre beta 1-HDL. Biochim Biophys Acta 1301:255–262

    PubMed  Google Scholar 

  102. Jiang XC, Bruce C, Mar J, Lin M, Ji Y, Francone OL, Tall AR (1999) Targeted mutation of plasma phospholipid transfer protein gene markedly reduces high-density lipoprotein levels. J Clin Invest 103:907–914

    PubMed  CAS  Google Scholar 

  103. Krieger M (1999) Charting the fate of the “good cholesterol”: identification and characterization of the high-density lipoprotein receptor SR-BI. Annu Rev Biochem 68:523–558

    Article  PubMed  CAS  Google Scholar 

  104. Acton S, Rigotti A, Landschulz KT, Xu S, Hobbs HH, Krieger M (1996) Identification of scavenger receptor SR-BI as a high density lipoprotein receptor. Science 271:518–520

    PubMed  CAS  Google Scholar 

  105. Rigotti A, Trigatti B, Babitt J, Penman M, Xu S, Krieger M (1997) Scavenger receptor BI-a cell surface receptor for high density lipoprotein. Curr Opin Lipidol 8:181–188

    PubMed  CAS  Google Scholar 

  106. Cao G, Garcia CK, Wyne KL, Schultz RA, Parker KL, Hobbs HH (1997) Structure and localization of the human gene encoding SR-BI/CLA-1. Evidence for transcriptional control by steroidogenic factor 1. J Biol Chem 272:33068–33076

    Article  PubMed  CAS  Google Scholar 

  107. Murao K, Terpstra V, Green SR, Kondratenko N, Steinberg D, Quehenberger O (1997) Characterization of CLA-1, a human homologue of rodent scavenger receptor BI, as a receptor for high density lipoprotein and apoptotic thymocytes. J Biol Chem 272:17551–17557

    Article  PubMed  CAS  Google Scholar 

  108. Husemann J, Silverstein SC (2001) Expression of scavenger receptor class B, type I, by astrocytes and vascular smooth muscle cells in normal adult mouse and human brain and in Alzheimer’s disease brain. Am J Pathol 158:825–832

    PubMed  CAS  Google Scholar 

  109. Srivastava RA (2003) Scavenger receptor class B type I expression in murine brain and regulation by estrogen and dietary cholesterol. J Neurol Sci 210:11–18

    Article  PubMed  CAS  Google Scholar 

  110. Babitt J, Trigatti B, Rigotti A, Smart EJ, Anderson RG, Xu S, Krieger M (1997) Murine SR-BI, a high density lipoprotein receptor that mediates selective lipid uptake, is N-glycosylated and fatty acylated and colocalizes with plasma membrane caveolae. J Biol Chem 272:13242–13249

    Article  PubMed  CAS  Google Scholar 

  111. Graf GA, Connell PM, van der Westhuyzen DR, Smart EJ (1999) The class B, type I scavenger receptor promotes the selective uptake of high density lipoprotein cholesterol ethers into caveolae. J Biol Chem 274:12043–12048

    Article  PubMed  CAS  Google Scholar 

  112. Matveev S, van der Westhuyzen DR, Smart EJ (1999) Co-expression of scavenger receptor-BI and caveolin-1 is associated with enhanced selective cholesteryl ester uptake in THP-1 macrophages. J Lipid Res 40:1647–1654

    PubMed  CAS  Google Scholar 

  113. Reaven E, Nomoto A, Leers-Sucheta S, Temel R, Williams DL, Azhar S (1998) Expression and microvillar localization of scavenger receptor, class B, type I (a high density lipoprotein receptor) in luteinized and hormone-desensitized rat ovarian models. Endocrinology 139:2847–2856

    Article  PubMed  CAS  Google Scholar 

  114. Williams DL, Wong JS, Hamilton RL (2002) SR-BI is required for microvillar channel formation and the localization of HDL particles to the surface of adrenocortical cells in vivo. J Lipid Res 43:544–549

    PubMed  CAS  Google Scholar 

  115. Peng Y, Akmentin W, Connelly MA, Lund-Katz S, Phillips MC, Williams DL (2004) Scavenger receptor BI (SR-BI) clustered on microvillar extensions suggests that this plasma membrane domain is a way station for cholesterol trafficking between cells and high-density lipoprotein. Mol Biol Cell 15:384–396

    Article  PubMed  CAS  Google Scholar 

  116. Silver DL (2002) A carboxyl-terminal PDZ-interacting domain of scavenger receptor B, type I is essential for cell surface expression in liver. J Biol Chem 277:34042–34047

    Article  PubMed  CAS  Google Scholar 

  117. Ikemoto M, Arai H, Feng D, Tanaka K, Aoki J, Dohmae N, Takio K, Adachi H, Tsujimoto M, Inoue K (2000) Identification of a PDZ-domain-containing protein that interacts with the scavenger receptor class B type I. Proc Natl Acad Sci U S A 97:6538–6543

    Article  PubMed  CAS  Google Scholar 

  118. Kocher O, Yesilaltay A, Cirovic C, Pal R, Rigotti A, Krieger M (2003) Targeted disruption of the PDZK1 gene in mice causes tissue-specific depletion of the HDL Receptor SR-BI and altered lipoprotein metabolism. J Biol Chem 278:52820–52825

    Article  PubMed  CAS  Google Scholar 

  119. Acton SL, Scherer PE, Lodish HF, Krieger M (1994) Expression cloning of SR-BI, a CD36-related class B scavenger receptor. J Biol Chem 269:21003–21009

    PubMed  CAS  Google Scholar 

  120. Calvo D, Gomez-Coronado D, Suarez Y, Lasuncion MA, Vega MA (1998) Human CD36 is a high affinity receptor for the native lipoproteins HDL, LDL, and VLDL. J Lipid Res 39:777–788

    PubMed  CAS  Google Scholar 

  121. Liadaki KN, Liu T, Xu S, Ishida BY, Duchateaux PN, Krieger JP, Kane J, Krieger M, Zannis VI (2000) Binding of high density lipoprotein (HDL) and discoidal reconstituted HDL to the HDL receptor scavenger receptor class B type I. Effect of lipid association and APOA-I mutations on receptor binding. J Biol Chem 275:21262–21271

    Article  PubMed  CAS  Google Scholar 

  122. Xu S, Laccotripe M, Huang X, Rigotti A, Zannis VI, Krieger M (1997) Apolipoproteins of HDL can directly mediate binding to the scavenger receptor SR-BI, an HDL receptor that mediates selective lipid uptake. J Lipid Res 38:1289–1298

    PubMed  CAS  Google Scholar 

  123. Cai L, de Beer MC, de Beer FC, van der Westhuyzen DR (2005) Serum amyloid A is a ligand for scavenger receptor class B type I and inhibits high density lipoprotein binding and selective lipid uptake. J Biol Chem 280:2954–2961

    Article  PubMed  CAS  Google Scholar 

  124. Urban S, Zieseniss S, Werder M, Hauser H, Budzinski R, Engelmann B (2000) Scavenger receptor BI transfers major lipoprotein-associated phospholipids into the cells. J Biol Chem 275:33409–33415

    Article  PubMed  CAS  Google Scholar 

  125. Thuahnai ST, Lund-Katz S, Williams DL, Phillips MC (2001) Scavenger receptor class B, type I-mediated uptake of various lipids into cells. Influence of the nature of the donor particle interaction with the receptor. J Biol Chem 276:43801–43808

    Article  PubMed  CAS  Google Scholar 

  126. Greene DJ, Skeggs JW, Morton RE (2001) Elevated triglyceride content diminishes the capacity of high density lipoprotein to deliver cholesteryl esters via the scavenger receptor class B type I (SR-BI). J Biol Chem 276:4804–4811

    Article  PubMed  CAS  Google Scholar 

  127. Stangl H, Hyatt M, Hobbs HH (1999) Transport of lipids from high and low density lipoproteins via scavenger receptor-BI. J Biol Chem 274:32692–32698

    Article  PubMed  CAS  Google Scholar 

  128. Swarnakar S, Temel RE, Connelly MA, Azhar S, Williams DL (1999) Scavenger receptor class B, type I, mediates selective uptake of low density lipoprotein cholesteryl ester. J Biol Chem 274:29733–29739

    Article  PubMed  CAS  Google Scholar 

  129. Gu X, Lawrence R, Krieger M (2000) Dissociation of the high density lipoprotein and low density lipoprotein binding activities of murine scavenger receptor class B type I (mSR-BI) using retrovirus library-based activity dissection. J Biol Chem 275:9120–9130

    Article  PubMed  CAS  Google Scholar 

  130. Gu X, Trigatti B, Xu S, Acton S, Babitt J, Krieger M (1998) The efficient cellular uptake of high density lipoprotein lipids via scavenger receptor class B type I requires not only receptor-mediated surface binding but also receptor-specific lipid transfer mediated by its extracellular domain. J Biol Chem 273:26338–26348

    Article  PubMed  CAS  Google Scholar 

  131. Ji Y, Jian B, Wang N, Sun Y, Moya ML, Phillips MC, Rothblat GH, Swaney JB, Tall AR (1997) Scavenger receptor BI promotes high density lipoprotein-mediated cellular cholesterol efflux. J Biol Chem 272:20982–20985

    Article  PubMed  CAS  Google Scholar 

  132. Gu X, Kozarsky K, Krieger M (2000) Scavenger receptor class B, type I-mediated [3H]cholesterol efflux to high and low density lipoproteins is dependent on lipoprotein binding to the receptor. J Biol Chem 275:29993–30001

    Article  PubMed  CAS  Google Scholar 

  133. Parathath S, Sahoo D, Darlington YF, Peng Y, Collins HL, Rothblat GH, Williams DL, Connelly MA (2004) Glycine 420 near the C-terminal transmembrane domain of SR-BI is critical for proper delivery and metabolism of high density lipoprotein cholesteryl ester. J Biol Chem 279:24976–24985

    Article  PubMed  CAS  Google Scholar 

  134. Liu B, Krieger M (2002) Highly purified scavenger receptor class B, type I reconstituted into phosphatidylcholine/cholesterol liposomes mediates high affinity high density lipoprotein binding and selective lipid uptake. J Biol Chem 277:34125–34135

    Article  PubMed  CAS  Google Scholar 

  135. Liu T, Krieger M, Kan HY, Zannis VI (2002) The effects of mutations in helices 4 and 6 of apoA-I on scavenger receptor class B type I (SR-BI)-mediated cholesterol efflux suggest that formation of a productive complex between reconstituted high density lipoprotein and SR-BI is required for efficient lipid transport. J Biol Chem 277:21576–21584

    Article  PubMed  CAS  Google Scholar 

  136. Llera-Moya M, Rothblat GH, Connelly MA, Kellner-Weibel G, Sakr SW, Phillips MC, Williams DL (1999) Scavenger receptor BI (SR-BI) mediates free cholesterol flux independently of HDL tethering to the cell surface. J Lipid Res 40:575–580

    PubMed  Google Scholar 

  137. Nieland TJ, Penman M, Dori L, Krieger M, Kirchhausen T (2002) Discovery of chemical inhibitors of the selective transfer of lipids mediated by the HDL receptor SR-BI. Proc Natl Acad Sci U S A 99:15422–15427

    Article  PubMed  CAS  Google Scholar 

  138. Connelly MA, Llera-Moya M, Peng Y, Drazul-Schrader D, Rothblat GH, Williams DL (2003) Separation of lipid transport functions by mutations in the extracellular domain of scavenger receptor class B, type I. J Biol Chem 278:25773–25782

    Article  PubMed  CAS  Google Scholar 

  139. Wang N, Arai T, Ji Y, Rinninger F, Tall AR (1998) Liver-specific overexpression of scavenger receptor BI decreases levels of very low density lipoprotein ApoB, low density lipoprotein ApoB, and high density lipoprotein in transgenic mice. J Biol Chem 273:32920–32926

    Article  PubMed  CAS  Google Scholar 

  140. Ueda Y, Royer L, Gong E, Zhang J, Cooper PN, Francone O, Rubin EM (1999) Lower plasma levels and accelerated clearance of high density lipoprotein (HDL) and non-HDL cholesterol in scavenger receptor class B type I transgenic mice. J Biol Chem 274:7165–7171

    Article  PubMed  CAS  Google Scholar 

  141. Rigotti A, Trigatti BL, Penman M, Rayburn H, Herz J, Krieger M (1997) A targeted mutation in the murine gene encoding the high density lipoprotein (HDL) receptor scavenger receptor class B type I reveals its key role in HDL metabolism. Proc Natl Acad Sci U S A 94:12610–12615

    Article  PubMed  CAS  Google Scholar 

  142. Out R, Hoekstra M, Spijkers JA, Kruijt JK, Van Eck M, Bos IS, Twisk J, van Berkel TJ (2004) Scavenger receptor class B type I is solely responsible for the selective uptake of cholesteryl esters from HDL by the liver and the adrenals in mice. J Lipid Res 45:2088–2095

    Article  PubMed  CAS  Google Scholar 

  143. Out R, Kruijt JK, Rensen PC, Hildebrand RB, De Vos P, Van Eck M, van Berkel TJ (2004) Scavenger receptor BI plays a role in facilitating chylomicron metabolism. J Biol Chem 279:18401–18406

    Article  PubMed  CAS  Google Scholar 

  144. Out R, Hoekstra M, de Jager SC, Vos PD, van der Westhuyzen DR, Webb NR, Van Eck M, Biessen EA, van Berkel TJ (2005) Adenovirus-mediated hepatic overexpression of scavenger receptor BI accelerates chylomicron metabolism in C57BL/6J mice. J Lipid Res 46:1172–1181

    Article  PubMed  CAS  Google Scholar 

  145. Mardones P, Quinones V, Amigo L, Moreno M, Miquel JF, Schwarz M, Miettinen HE, Trigatti B, Krieger M, VanPatten S, Cohen DE, Rigotti A (2001) Hepatic cholesterol and bile acid metabolism and intestinal cholesterol absorption in scavenger receptor class B type I-deficient mice. J Lipid Res 42:170–180

    PubMed  CAS  Google Scholar 

  146. Trigatti B, Rayburn H, Vinals M, Braun A, Miettinen H, Penman M, Hertz M, Schrenzel M, Amigo L, Rigotti A, Krieger M (1999) Influence of the high density lipoprotein receptor SR-BI on reproductive and cardiovascular pathophysiology. Proc Natl Acad Sci U S A 96:9322–9327

    Article  PubMed  CAS  Google Scholar 

  147. Holm TM, Braun A, Trigatti BL, Brugnara C, Sakamoto M, Krieger M, Andrews NC (2002) Failure of red blood cell maturation in mice with defects in the high-density lipoprotein receptor SR-BI. Blood 99:1817–1824

    Article  PubMed  CAS  Google Scholar 

  148. Yesilaltay A, Morales MG, Amigo L, Zanlugo S, Rigotti A, Karackattu SL, Donahee MH, Kozarsky KF, Krieger M (2006) Effects of hepatic expression of the HDL receptor SR-BI on lipoprotein metabolism and female fertility. Endocrinology (Jan. 12) (Epub ahead of print)

  149. Mineo C, Yuhanna IS, Quon MJ, Shaul PW (2003) High density lipoprotein-induced endothelial nitric-oxide synthase activation is mediated by Akt and MAP kinases. J Biol Chem 278:9142–9149

    Article  PubMed  CAS  Google Scholar 

  150. Shaul PW (2003) Endothelial nitric oxide synthase, caveolae and the development of atherosclerosis. J Physiol 547:21–33

    Article  PubMed  CAS  Google Scholar 

  151. Yuhanna IS, Zhu Y, Cox BE, Hahner LD, Osborne-Lawrence S, Lu P, Marcel YL, Anderson RG, Mendelsohn ME, Hobbs HH, Shaul PW (2001) High-density lipoprotein binding to scavenger receptor-BI activates endothelial nitric oxide synthase. Nat Med 7:853–857

    Article  PubMed  CAS  Google Scholar 

  152. Li XA, Titlow WB, Jackson BA, Giltiay N, Nikolova-Karakashian M, Uittenbogaard A, Smart EJ (2002) High density lipoprotein binding to scavenger receptor, class B, type I activates endothelial nitric-oxide synthase in a ceramide-dependent manner. J Biol Chem 277:11058–11063

    Article  PubMed  CAS  Google Scholar 

  153. Gong M, Wilson M, Kelly T, Su W, Dressman J, Kincer J, Matveev SV, Guo L, Guerin T, Li XA, Zhu W, Uittenbogaard A, Smart EJ (2003) HDL-associated estradiol stimulates endothelial NO synthase and vasodilation in an SR-BI-dependent manner. J Clin Invest 111:1579–1587

    Article  PubMed  CAS  Google Scholar 

  154. Li XA, Guo L, Dressman JL, Asmis R, Smart EJ (2005) A novel ligand-independent apoptotic pathway induced by SR-BI and suppressed by eNOS and HDL. J Biol Chem 280:19087–19096

    Article  PubMed  CAS  Google Scholar 

  155. Huszar D, Varban ML, Rinninger F, Feeley R, Arai T, Fairchild-Huntress V, Donovan MJ, Tall AR (2000) Increased LDL cholesterol and atherosclerosis in LDL receptor-deficient mice with attenuated expression of scavenger receptor B1. Arterioscler Thromb Vasc Biol 20:1068–1073

    PubMed  CAS  Google Scholar 

  156. Arai T, Wang N, Bezouevski M, Welch C, Tall AR (1999) Decreased atherosclerosis in heterozygous low density lipoprotein receptor-deficient mice expressing the scavenger receptor BI transgene. J Biol Chem 274:2366–2371

    Article  PubMed  CAS  Google Scholar 

  157. Ueda Y, Gong E, Royer L, Cooper PN, Francone OL, Rubin EM (2000) Relationship between expression levels and atherogenesis in scavenger receptor class B, type I transgenics. J Biol Chem 275:20368–20373

    Article  PubMed  CAS  Google Scholar 

  158. Kozarsky KF, Donahee MH, Glick JM, Krieger M, Rader DJ (2000) Gene transfer and hepatic overexpression of the HDL receptor SR-BI reduces atherosclerosis in the cholesterol-fed LDL receptor-deficient mouse. Arterioscler Thromb Vasc Biol 20:721–727

    PubMed  CAS  Google Scholar 

  159. Braun A, Trigatti BL, Post MJ, Sato K, Simons M, Edelberg JM, Rosenberg RD, Schrenzel M, Krieger M (2002) Loss of SR-BI expression leads to the early onset of occlusive atherosclerotic coronary artery disease, spontaneous myocardial infarctions, severe cardiac dysfunction, and premature death in apolipoprotein E-deficient mice. Circ Res 90:270–276

    Article  PubMed  CAS  Google Scholar 

  160. Braun A, Zhang S, Miettinen HE, Ebrahim S, Holm TM, Vasile E, Post MJ, Yoerger DM, Picard MH, Krieger JL, Andrews NC, Simons M, Krieger M (2003) Probucol prevents early coronary heart disease and death in the high-density lipoprotein receptor SR-BI/apolipoprotein E double knockout mouse. Proc Natl Acad Sci U S A 100:7283–7288

    Article  PubMed  CAS  Google Scholar 

  161. Karackattu SL, Picard MH, Krieger M (2005) Lymphocytes are not required for the rapid onset of coronary heart disease in scavenger receptor class B type I/apolipoprotein E double knockout mice. Arterioscler Thromb Vasc Biol 25:803–808

    Article  PubMed  CAS  Google Scholar 

  162. Karackattu SL, Trigatti B, Krieger M (2006) Hepatic lipase delays atherosclerosis, myocardial infarction and cardiac dysfunction and extends lifespan in SR-BI/apolipoprotein E double knockout mice. Arterioscler. Thromb Vasc Biol (Jan. 5) (Epub ahead of print)

  163. Zhang S, Picard MH, Vasile E, Zhu Y, Raffai RL, Weisgraber KH, Krieger M (2005) Diet-induced occlusive coronary atherosclerosis, myocardial infarction, cardiac dysfunction and premature death in SR-BI-deficient, hypomorphic apolipoprotein ER61 mice. Circulation 111:3457–3464

    Article  PubMed  CAS  Google Scholar 

  164. Webb NR, de Beer MC, Yu J, Kindy MS, Daugherty A, van der Westhuyzen DR, de Beer FC (2002) Overexpression of SR-BI by adenoviral vector promotes clearance of apoA-I, but not apoB, in human apoB transgenic mice. J Lipid Res 43:1421–1428

    Article  PubMed  CAS  Google Scholar 

  165. Ji Y, Wang N, Ramakrishnan R, Sehayek E, Huszar D, Breslow JL, Tall AR (1999) Hepatic scavenger receptor BI promotes rapid clearance of high density lipoprotein free cholesterol and its transport into bile. J Biol Chem 274:33398–33402

    Article  PubMed  CAS  Google Scholar 

  166. Oldfield S, Lowry C, Ruddick J, Lightman S (2002) ABCG4: a novel human white family ABC-transporter expressed in the brain and eye. Biochim Biophys Acta 1591:175–179

    Article  PubMed  CAS  Google Scholar 

  167. Klucken J, Buchler C, Orso E, Kaminski WE, Porsch-Ozcurumez M, Liebisch G, Kapinsky M, Diederich W, Drobnik W, Dean M, Allikmets R, Schmitz G (2000) ABCG1 (ABC8), the human homolog of the Drosophila white gene, is a regulator of macrophage cholesterol and phospholipid transport. Proc Natl Acad Sci U S A 97:817–822

    Article  PubMed  CAS  Google Scholar 

  168. Savary S, Denizot F, Luciani M, Mattei M, Chimini G (1996) Molecular cloning of a mammalian ABC transporter homologous to Drosophila white gene. Mamm Genome 7:673–676

    Article  PubMed  CAS  Google Scholar 

  169. Croop JM, Tiller GE, Fletcher JA, Lux ML, Raab E, Goldenson D, Son D, Arciniegas S, Wu RL (1997) Isolation and characterization of a mammalian homolog of the Drosophila white gene. Gene 185:77–85

    Article  PubMed  CAS  Google Scholar 

  170. Nakamura K, Kennedy MA, Baldan A, Bojanic DD, Lyons K, Edwards PA (2004) Expression and regulation of multiple murine ATP-binding cassette transporter G1 mRNAs/isoforms that stimulate cellular cholesterol efflux to high density lipoprotein. J Biol Chem 279:45980–45989

    Article  PubMed  CAS  Google Scholar 

  171. Venkateswaran A, Repa JJ, Lobaccaro JM, Bronson A, Mangelsdorf DJ, Edwards PA (2000) Human white/murine ABC8 mRNA levels are highly induced in lipid-loaded macrophages. A transcriptional role for specific oxysterols. J Biol Chem 275:14700–14707

    Article  PubMed  CAS  Google Scholar 

  172. Tangirala RK, Bischoff ED, Joseph SB, Wagner BL, Walczak R, Laffitte BA, Daige CL, Thomas D, Heyman RA, Mangelsdorf DJ, Wang X, Lusis AJ, Tontonoz P, Schulman IG (2002) Identification of macrophage liver X receptors as inhibitors of atherosclerosis. Proc Natl Acad Sci U S A 99:11896–11901

    Article  PubMed  CAS  Google Scholar 

  173. Vaughan AM, Oram JF (2005) ABCG1 redistributes cell cholesterol to domains removable by high density lipoprotein but not by lipid-depleted apolipoproteins. J Biol Chem 280:30150–30157

    Article  PubMed  CAS  Google Scholar 

  174. Kennedy MA, Barrera GC, Nakamura K, Baldan A, Tarr P, Fishbein MC, Frank J, Francone OL, Edwards PA (2005) ABCG1 has a critical role in mediating cholesterol efflux to HDL and preventing cellular lipid accumulation. Cell Metab 1:121–131

    Article  PubMed  CAS  Google Scholar 

  175. Zannis VI, Kypreos KE, Chroni A, Kardassis D, Zanni EE (2004) Lipoproteins and atherogenesis. In: Loscalzo J (ed) Molecular mechanisms of atherosclerosis, pp 111–174

  176. Melchior GW, Castle CK, Murray RW, Blake WL, Dinh DM, Marotti KR (1994) Apolipoprotein A-I metabolism in cholesteryl ester transfer protein transgenic mice. Insights into the mechanisms responsible for low plasma high density lipoprotein levels. J Biol Chem 269:8044–8051

    PubMed  CAS  Google Scholar 

  177. Plump AS, Masucci-Magoulas L, Bruce C, Bisgaier CL, Breslow JL, Tall AR (1999) Increased atherosclerosis in ApoE and LDL receptor gene knock-out mice as a result of human cholesteryl ester transfer protein transgene expression. Arterioscler Thromb Vasc Biol 19:1105–1110

    PubMed  CAS  Google Scholar 

  178. Jiang XC, Qin S, Qiao C, Kawano K, Lin M, Skold A, Xiao X, Tall AR (2001) Apolipoprotein B secretion and atherosclerosis are decreased in mice with phospholipid-transfer protein deficiency. Nat Med 7:847–852

    Article  PubMed  CAS  Google Scholar 

  179. Homanics GE, de Silva HV, Osada J, Zhang SH, Wong H, Borensztajn J, Maeda N (1995) Mild dyslipidemia in mice following targeted inactivation of the hepatic lipase gene. J Biol Chem 270:2974–2980

    Article  PubMed  CAS  Google Scholar 

  180. Mezdour H, Jones R, Dengremont C, Castro G, Maeda N (1997) Hepatic lipase deficiency increases plasma cholesterol but reduces susceptibility to atherosclerosis in apolipoprotein E-deficient mice. J Biol Chem 272:13570–13575

    Article  PubMed  CAS  Google Scholar 

  181. Ishida T, Choi S, Kundu RK, Hirata K, Rubin EM, Cooper AD, Quertermous T (2003) Endothelial lipase is a major determinant of HDL level. J Clin Invest 111:347–355

    Article  PubMed  CAS  Google Scholar 

  182. Ma K, Cilingiroglu M, Otvos JD, Ballantyne CM, Marian AJ, Chan L (2003) Endothelial lipase is a major genetic determinant for high-density lipoprotein concentration, structure, and metabolism. Proc Natl Acad Sci U S A 100:2748–2753

    Article  PubMed  CAS  Google Scholar 

  183. Ishida T, Choi SY, Kundu RK, Spin J, Yamashita T, Hirata K, Kojima Y, Yokoyama M, Cooper AD, Quertermous T (2004) Endothelial lipase modulates susceptibility to atherosclerosis in apolipoprotein-E-deficient mice. J Biol Chem 279:45085–45092

    Article  PubMed  CAS  Google Scholar 

  184. Barter PJ, Brewer HB Jr, Chapman MJ, Hennekens CH, Rader DJ, Tall AR (2003) Cholesteryl ester transfer protein: a novel target for raising HDL and inhibiting atherosclerosis. Arterioscler Thromb Vasc Biol 23:160–167

    Article  PubMed  CAS  Google Scholar 

  185. Inazu A, Brown ML, Hesler CB, Agellon LB, Koizumi J, Takata K, Maruhama Y, Mabuchi H, Tall AR (1990) Increased high-density lipoprotein levels caused by a common cholesteryl-ester transfer protein gene mutation. N Engl J Med 323:1234–1238

    Article  PubMed  CAS  Google Scholar 

  186. Maruyama T, Sakai N, Ishigami M, Hirano K, Arai T, Okada S, Okuda E, Ohya A, Nakajima N, Kadowaki K, Fushimi E, Yamashita S, Matsuzawa Y (2003) Prevalence and phenotypic spectrum of cholesteryl ester transfer protein gene mutations in Japanese hyperalphalipoproteinemia. Atherosclerosis 166:177–185

    Article  PubMed  CAS  Google Scholar 

  187. Tall AR, Forester LR, Bongiovanni GL (1983) Facilitation of phosphatidylcholine transfer into high density lipoproteins by an apolipoprotein in the density 1.20–1.26 g/ml fraction of plasma. J Lipid Res 24:277–289

    PubMed  CAS  Google Scholar 

  188. Huuskonen J, Olkkonen VM, Jauhiainen M, Ehnholm C (2001) The impact of phospholipid transfer protein (PLTP) on HDL metabolism. Atherosclerosis 155:269–281

    Article  PubMed  CAS  Google Scholar 

  189. Tollefson JH, Ravnik S, Albers JJ (1988) Isolation and characterization of a phospholipid transfer protein (LTP-II) from human plasma. J Lipid Res 29:1593–1602

    PubMed  CAS  Google Scholar 

  190. Krauss RM, Levy RI, Fredrickson DS (1974) Selective measurement of two lipase activities in postheparin plasma from normal subjects and patients with hyperlipoproteinemia. J Clin Invest 54:1107–1124

    PubMed  CAS  Google Scholar 

  191. Breckenridge WC, Little JA, Alaupovic P, Wang CS, Kuksis A, Kakis G, Lindgren F, Gardiner G (1982) Lipoprotein abnormalities associated with a familial deficiency of hepatic lipase. Atherosclerosis 45:161–179

    Article  PubMed  CAS  Google Scholar 

  192. Navab M, Hama SY, Anantharamaiah GM, Hassan K, Hough GP, Watson AD, Reddy ST, Sevanian A, Fonarow GC, Fogelman AM (2000) Normal high density lipoprotein inhibits three steps in the formation of mildly oxidized low density lipoprotein: steps 2 and 3. J Lipid Res 41:1495–1508

    PubMed  CAS  Google Scholar 

  193. Navab M, Hama SY, Cooke CJ, Anantharamaiah GM, Chaddha M, Jin L, Subbanagounder G, Faull KF, Reddy ST, Miller NE, Fogelman AM (2000) Normal high density lipoprotein inhibits three steps in the formation of mildly oxidized low density lipoprotein: step 1. J Lipid Res 41:1481–1494

    PubMed  CAS  Google Scholar 

  194. Mackness MI, Arrol S, Durrington PN (1991) Paraoxonase prevents accumulation of lipoperoxides in low-density lipoprotein. FEBS Lett 286:152–154

    Article  PubMed  CAS  Google Scholar 

  195. Watson AD, Navab M, Hama SY, Sevanian A, Prescott SM, Stafforini DM, McIntyre TM, Du BN, Fogelman AM, Berliner JA (1995) Effect of platelet activating factor-acetylhydrolase on the formation and action of minimally oxidized low density lipoprotein. J Clin Invest 95:774–782

    PubMed  CAS  Google Scholar 

  196. Watson AD, Berliner JA, Hama SY, La Du BN, Faull KF, Fogelman AM, Navab M (1995) Protective effect of high density lipoprotein associated paraoxonase. Inhibition of the biological activity of minimally oxidized low density lipoprotein. J Clin Invest 96:2882–2891

    PubMed  CAS  Google Scholar 

  197. Rader DJ (2002) High-density lipoproteins and atherosclerosis. Am J Cardiol 90:62i–70i

    Article  PubMed  CAS  Google Scholar 

  198. Ansell BJ, Navab M, Hama S, Kamranpour N, Fonarow G, Hough G, Rahmani S, Mottahedeh R, Dave R, Reddy ST, Fogelman AM (2003) Inflammatory/antiinflammatory properties of high-density lipoprotein distinguish patients from control subjects better than high-density lipoprotein cholesterol levels and are favorably affected by simvastatin treatment. Circulation 108:2751–2756

    Article  PubMed  CAS  Google Scholar 

  199. Navab M, Hama SY, Hough GP, Subbanagounder G, Reddy ST, Fogelman AM (2001) A cell-free assay for detecting HDL that is dysfunctional in preventing the formation of or inactivating oxidized phospholipids. J Lipid Res 42:1308–1317

    PubMed  CAS  Google Scholar 

  200. Miller M, Rhyne J, Hamlette S, Birnbaum J, Rodriguez A (2003) Genetics of HDL regulation in humans. Curr Opin Lipidol 14:273–279

    Article  PubMed  CAS  Google Scholar 

  201. Ikewaki K, Matsunaga A, Han H, Watanabe H, Endo A, Tohyama J, Kuno M, Mogi J, Sugimoto K, Tada N, Sasaki J, Mochizuki S (2004) A novel two nucleotide deletion in the apolipoprotein A-I gene, apoA-I Shinbashi, associated with high density lipoprotein deficiency, corneal opacities, planar xanthomas, and premature coronary artery disease. Atherosclerosis 172:39–45

    Article  PubMed  CAS  Google Scholar 

  202. Yokota H, Hashimoto Y, Okubo S, Yumoto M, Mashige F, Kawamura M, Kotani K, Usuki Y, Shimada S, Kitamura K, Nakahara K (2002) Apolipoprotein A-I deficiency with accumulated risk for CHD but no symptoms of CHD. Atherosclerosis 162:399–407

    Article  PubMed  CAS  Google Scholar 

  203. Pisciotta L, Miccoli R, Cantafora A, Calabresi L, Tarugi P, Alessandrini P, Bittolo BG, Franceschini G, Cortese C, Calandra S, Bertolini S (2003) Recurrent mutations of the apolipoprotein A-I gene in three kindreds with severe HDL deficiency. Atherosclerosis 167:335–345

    Article  PubMed  CAS  Google Scholar 

  204. Singaraja RR, Brunham LR, Visscher H, Kastelein JJ, Hayden MR (2003) Efflux and atherosclerosis: the clinical and biochemical impact of variations in the ABCA1 gene. Arterioscler Thromb Vasc Biol 23:1322–1332

    Article  PubMed  CAS  Google Scholar 

  205. Clee SM, Kastelein JJ, van Dam M, Marcil M, Roomp K, Zwarts KY, Collins JA, Roelants R, Tamasawa N, Stulc T, Suda T, Ceska R, Boucher B, Rondeau C, DeSouich C, Brooks-Wilson A, Molhuizen HO, Frohlich J, Genest J Jr, Hayden MR (2000) Age and residual cholesterol efflux affect HDL cholesterol levels and coronary artery disease in ABCA1 heterozygotes. J Clin Invest 106:1263–1270

    PubMed  CAS  Google Scholar 

  206. Hirano K, Yamashita S, Kuga Y, Sakai N, Nozaki S, Kihara S, Arai T, Yanagi K, Takami S, Menju M (1995) Atherosclerotic disease in marked hyperalphalipoproteinemia. Combined reduction of cholesteryl ester transfer protein and hepatic triglyceride lipase. Arterioscler Thromb Vasc Biol 15:1849–1856

    PubMed  CAS  Google Scholar 

  207. Zhong S, Sharp DS, Grove JS, Bruce C, Yano K, Curb JD, Tall AR (1996) Increased coronary heart disease in Japanese-American men with mutation in the cholesteryl ester transfer protein gene despite increased HDL levels. J Clin Invest 97:2917–2923

    Article  PubMed  CAS  Google Scholar 

  208. Hirano K, Yamashita S, Nakajima N, Arai T, Maruyama T, Yoshida Y, Ishigami M, Sakai N, Kameda-Takemura K, Matsuzawa Y (1997) Genetic cholesteryl ester transfer protein deficiency is extremely frequent in the Omagari area of Japan. Marked hyperalphalipoproteinemia caused by CETP gene mutation is not associated with longevity. Arterioscler Thromb Vasc Biol 17:1053–1059

    PubMed  CAS  Google Scholar 

  209. van Dam MJ, de Groot E, Clee SM, Hovingh GK, Roelants R, Brooks-Wilson A, Zwinderman AH, Smit AJ, Smelt AH, Groen AK, Hayden MR, Kastelein JJ (2002) Association between increased arterial-wall thickness and impairment in ABCA1-driven cholesterol efflux: an observational study. Lancet 359:37–42

    Article  PubMed  Google Scholar 

  210. Brousseau ME, Schaefer EJ, Wolfe ML, Bloedon LT, Digenio AG, Clark RW, Mancuso JP, Rader DJ (2004) Effects of an inhibitor of cholesteryl ester transfer protein on HDL cholesterol. N Engl J Med 350:1505–1515

    Article  PubMed  CAS  Google Scholar 

  211. de Grooth GJ, Kuivenhoven JA, Stalenhoef AF, de Graaf J, Zwinderman AH, Posma JL, van Tol A, Kastelein JJ (2002) Efficacy and safety of a novel cholesteryl ester transfer protein inhibitor, JTT-705, in humans: a randomized phase II dose–response study. Circulation 105:2159–2165

    Article  PubMed  CAS  Google Scholar 

  212. Gorshkova IN, Liu T, Zannis VI, Atkinson D (2002) Lipid-free structure and stability of apolipoprotein A-I: probing the central region by mutation. Biochemistry 41:10529–10539

    Article  PubMed  CAS  Google Scholar 

  213. Ajees AA, Anantharamaiah GM, Mishra VK, Hussain MM, Murthy HM (2006) Crystal structure of human apolipoprotein A-I: Insights into its protective effect against cardiovascular diseases. Proc Natl Acad Sci U S A (in press)

  214. Duong PT, Collins HL, Nickel M, Lund-Katz S, Rothblat GH, Phillips MC (2006) Characterization of nascent HDL particles and microparticles formed by ABCA1-mediated efflux of cellular lipids to ApoA-I. J Lipid Res (in press)

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Acknowledgements

We thank Anne Plunkett for preparing the manuscript. This work was supported by grants from the National Institutes of Health (HL33952, HL48739, HL68216, HL41484, HL66105, and HL52212).

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Authors and Affiliations

  1. Molecular Genetics, Whitaker Cardiovascular Institute and Department of Biochemistry, Boston University School of Medicine, Boston, MA, USA

    Vassilis I. Zannis & Angeliki Chroni

  2. Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA

    Monty Krieger

  3. Whitaker Cardiovascular Institute, Center for Advanced Biomedical Research, Boston University School of Medicine, 715 Albany Street W-509, Boston, MA, 02118, USA

    Vassilis I. Zannis

  4. Department of Biochemistry, University of Crete Medical School, Crete, Greece

    Vassilis I. Zannis

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  1. Vassilis I. Zannis
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  2. Angeliki Chroni
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Correspondence to Vassilis I. Zannis.

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Most recently the crystal structure of lipid-free apoA-I has been determined at 2.4Å resolution. The protein consists of a four helix N-terminal bundle and two C-terminal helices. The protein displays patches of positive and negative changes on the surface that may be important for its biological functions [213]. An attempt has been made to characterize particles released by J774 macrophages and human skin fibroblasts following interaction with apoA-I. In both cases, discoidal particles of α electrophoretic mobility of 9 nM and 12 nM diameter along with preβ1 particles, were produced. The 9 nM and 12 nM particles contain 2 and 3-4 apoA-I molecules per disc and there is no precursor product relationship between them [214].

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Zannis, V.I., Chroni, A. & Krieger, M. Role of apoA-I, ABCA1, LCAT, and SR-BI in the biogenesis of HDL. J Mol Med 84, 276–294 (2006). https://doi.org/10.1007/s00109-005-0030-4

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