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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2002;22:638.)
© 2002 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Opposite Effects of Plasma From Human Apolipoprotein A-II Transgenic Mice on Cholesterol Efflux From J774 Macrophages and Fu5AH Hepatoma Cells

Natalie Fournier; Anne Cogny; Véronique Atger; Danièle Pastier; Dominique Goudouneche; Antonino Nicoletti; Nicole Moatti; Jean Chambaz; Jean-Louis Paul; Athina-Despina Kalopissis

From the Laboratoire de Biochimie (N.F., D.G., N.M., J.-L.P.), Faculté des Sciences Pharmaceutiques, Châtenay-Malabry; Laboratoire de Biochimie (N.F., A.C., V.A., N.M., J.-L.P.), Hôpital Européen Georges Pompidou, AP-HP, Paris; U505 INSERM (D.P., J.C., A.-D.K.), Université Pierre et Marie Curie, Centre de Recherche des Cordeliers, Paris; and U430 INSERM (A.N.), Hôpital Broussais, AP-HP, Paris, France.

Correspondence to Dr N. Fournier, Laboratoire de Biochimie, Faculté des Sciences Pharmaceutiques, 5 rue JB Clément, 92296 Châtenay-Malabry, France. E-mail natalie_fournier{at}yahoo.fr

	Abstract

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Overexpression of human apolipoprotein A-II (hapo A-II) in transgenic mice (hAIItg mice) induced marked hypertriglyceridemia and low levels of plasma high density lipoprotein (HDL) with a high hapo A-II content. We sought to determine whether cholesterol efflux to plasma and HDL from these mice would be affected. In the Fu5AH cell system, plasma from hAIItg mice induced a markedly lower cholesterol efflux than did control plasma, in accordance with the dependence of efflux on HDL concentration. Moreover, HDLs from hAIItg mice were less effective acceptors than were control HDLs. In the J774 macrophage cell system, pretreatment with cAMP, which upregulates ATP binding cassette transporter 1, induced a marked increase in the efflux to hAIItg plasma as well as to purified hapo A-I and hapo A-II, whereas it had no effect on cholesterol efflux to control plasma. A strong positive correlation was established between percent cAMP stimulation of efflux and plasma hapo A-II concentration. The cAMP stimulation of efflux to hAIItg mouse plasma may be linked to the presence of pre-ß migrating HDL containing hapo A-II. Thus, despite lower HDL and apolipoprotein A-I contents, the increased ability of plasma from hAIItg mice to extract cholesterol from macrophage-like cells may have an antiatherogenic influence.

Key Words: human apolipoprotein A-II transgenic mice • Fu5AH rat hepatoma cells • J774 mouse macrophages • cholesterol efflux • ATP binding cassette transporter 1

	Introduction

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The negative correlation between plasma HDL concentration and the risk of cardiovascular disease has been partly attributed to the ability of HDL to stimulate reverse cholesterol transport (RCT) from peripheral tissues to the liver for recycling.^1,2 The first step of RCT is efflux of free cholesterol from cell membranes to the extracellular medium. A major research effort these last decades has established that at least 3 mechanisms are involved: a nonspecific and relatively inefficient aqueous diffusion pathway, which operates in all cells, and 2 regulated pathways, which are modulated by phospholipid (PL)-containing acceptor particles (such as HDL) or lipid-poor apolipoproteins.³ On the other hand, controversial results were obtained regarding the effect of the apolipoprotein composition of HDL, with some studies reporting a stimulation of cholesterol efflux by HDLs containing only apoA-I⁴ and other studies reporting HDL carrying apoA-I and apoA-II.⁵ Recently, the type of the acceptor particles was linked to the type of the receptors present in the various cells,³ thus identifying the following 2 specific efflux mechanisms involving (1) the scavenger receptor class B type I (SR-BI) and (2) the ATP binding cassette transporter 1 (ABCA1). Cholesterol molecules that desorb from cell membranes rich in SR-BI diffuse through the aqueous phase and associate with PL-containing acceptor particles, in proportion to PL content.⁶ Moreover, the ability of HDL and serum to stimulate cholesterol efflux from different cell types was correlated with the expression level of SR-BI.⁷ SR-BI is equally efficient at mediating the import and export of cholesterol to and from cells to lipoproteins and other acceptors.^7,8 By contrast, the unidirectional efflux of membrane cholesterol and PL of cells expressing ABCA1 is promoted by apolipoproteins in lipid-poor form but is little affected by HDLs, small unilamellar vesicles, bile acid micelles, or cyclodextrin.^9–11

ApoA-I is the major apolipoprotein component of HDL, and its role in RCT has been extensively studied. ApoA-II is the second most abundant HDL apolipoprotein, but its contribution to the function of HDL is controversial and poorly understood. We recently generated transgenic mice overexpressing human apolipoprotein (hapo) A-II, which display a marked hypertriglyceridemia and a great decrease in plasma HDL and apoA-I concentrations.¹² HDLs from our transgenic mice are characterized by an enrichment in triglycerides, the predominance of smaller sized particles (7.8- versus 10-nm diameter), a low apoA-I/apoA-II ratio, and the presence of pre-ß HDLs containing hapo A-II.¹³

Our aim was to investigate the ability of plasma from hapo A-II transgenic (hAIItg) mice to promote cholesterol efflux from 2 cell types representative of SR-BI–mediated or ABCA1-mediated cholesterol efflux. Fu5AH rat hepatoma cells, which have a high expression level of SR-BI and lack ABCA1,^7,10 were used to assess the contribution to cholesterol efflux of plasma PL-rich acceptors.^14–16 The ability of plasma with a high hapo A-II content to promote cellular cholesterol efflux was assessed by use of the J774 mouse macrophage cell system, which expresses SR-BI at very low levels.⁷ Exposure of J774 cells to cAMP upregulates the expression of ABCA1, which is closely correlated with increased cholesterol efflux to several unassociated apolipoproteins, such as apoA-I,¹⁷ apoE,¹⁸ and apoA-IV.⁹ Therefore, we compared the efflux capacity of purified hapo A-II with that of hapo A-I.

	Methods

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The Methods section can be accessed online at http://www.atvb.ahajournals.org.

	Results

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Plasma and HDL From hAIItg Mice Decrease Cholesterol Efflux From Fu5AH Cells
Because of the low plasma HDL content of hAIItg mice (two individual lines and ), we compared its ability to promote cholesterol efflux with that of control mouse plasma. After 4-hour incubations with 2.5% diluted plasma from animals fed ad libitum, the fractional cholesterol efflux was 36% and 57% lower in plasma from and mice, respectively, than in plasma from control mice (Table 1). To determine whether the low plasma concentration or the different properties of HDL from transgenic mice were responsible for the decreased cholesterol efflux, we compared HDL from transgenic and control mice fed ad libitum at the same HDL-PL concentration. HDL from transgenic mice displayed increased protein and triglyceride contents and decreased cholesteryl ester, resulting in a lower ratio of HDL–total lipid to protein (Table 2). Cholesterol efflux was greatest to control HDL and was inversely related to the level of hapo A-II expression in transgenic mice, displaying 25% and 50% decreases in HDL from and mice, respectively (Figure 1).

View this table: [in this window] [in a new window]   Table 1. Plasma and HDL Parameters and Efflux Capacity of Plasma From Control and hAIItg Mice in Fu5AH Cells

View this table: [in this window] [in a new window]   Table 2. Mass Composition of HDL Isolated From Control and hAIItg Mice

View larger version (16K): [in this window] [in a new window]   Figure 1. Efflux capacity of HDLs from control and hAIItg mice in Fu5AH cells. Values are mean±SD of 3 separate experiments, each using different HDL preparations (from 20 to 24 mice fed ad libitum per group). For each HDL-PL concentration, the fractional cholesterol efflux (%/4 hours) was the average of triplicate wells, as described in Methods. aP<0.05, bP<0.01, and cP<0.001 for transgenic vs control mice. xP<0.01 and yP<0.001 for hAIItg- vs hAIItg- mice. Solid square indicates control mice; solid circle, mice; and solid triangle, mice.

Plasma From hAIItg Mice Stimulates Cholesterol Efflux From J774 Cells
In a first attempt, we tested the same plasma pools used in Fu5AH cells for their capacity to promote cholesterol efflux from J774 cells. Surprisingly, we obtained the opposite effect, inasmuch as plasma pools from and mice exhibited a greater efflux capacity from cAMP-treated cells (0.72±0.02%, 1.18±0.05%, and 2.46±0.09% for control, , and mice, respectively). Therefore, we precisely documented this effect with plasma from individual mice and used the feeding-fasting transition as a means to modulate the plasma concentrations of hapo A-II, mouse apo A-I (mapo A-I), and HDL. Indeed, plasma hapo A-II from animals in the fasted state is decreased 2-fold, leading to concomitant increases in plasma HDL levels and in the ratio of apoA-I to A-II in HDL; conversely, hypertriglyceridemia is normalized.¹³ When cells were not pretreated with cAMP, the fractional efflux was comparable to plasma from all mouse groups (Table 3). Pretreatment of the cells with cAMP markedly increased the cholesterol efflux to plasma from fed transgenic animals, with 40% and 73% cAMP stimulations of efflux for and mice, respectively. Interestingly, plasma from fasted and mice, which have similar plasma hapo A-II concentrations, induced comparable cAMP stimulations of efflux. By contrast, the fractional efflux to control mouse plasma was not stimulated by cAMP. Linear regression analysis revealed a strong positive correlation between the percent cAMP stimulation of efflux and the plasma concentration of hapo A-II (see Figure I, which can be accessed online at http://atvb.ahajournals.org).

View this table: [in this window] [in a new window]   Table 3. Efflux Capacity of Plasma From Control and hAIItg Mice in J774 Cells

Hapo A-II and Hapo A-I Stimulate Cholesterol Efflux From J774 Cells
Because cholesterol efflux from J774 macrophages is enhanced in the presence of unassociated apolipoproteins^9,17,18 and because plasma from hAIItg mice has elevated concentrations of hapo A-II, we compared the efflux capacities of lipid-free hapo A-II and hapo A-I. In 3 separate experiments, marked cAMP stimulations of efflux were promoted by both apolipoproteins to similar degrees (Table 4). These values were very close to those previously obtained for hapo A-I and hapo A-IV.⁹

View this table: [in this window] [in a new window]   Table 4. Efflux Capacity of Human Lipid-Free ApoA-II and ApoA-I in J774 Cells

Pre-ß Migrating HDLs Containing Hapo A-II Are Present in Plasma of Transgenic Mice
Because pre-ß HDL is an efficient acceptor of cellular cholesterol, we analyzed the proportions of and pre-ß HDL in control and transgenic mice (Figure 2). In plasma from control mice either fed or fasted, the bulk of apoA-I was present in large-sized HDL and a very small amount in pre-ß HDL, whereas mapo A-II was present only in HDL (not shown). Plasma from fed or fasted mice contained 2 main HDL subpopulations with mobility; apoA-I was present in the larger HDL and in pre-ß HDL (not shown), whereas hapo A-II was present in all HDL subpopulations as well as in pre-ß HDL. Irrespective of nutritional state, plasma from mice contained little apoA-I in HDL (not shown), whereas hapo A-II was abundantly present in all HDL subfractions, especially in the smaller ones. For the fed state, pre-ß HDL with hapo A-II was more abundant in than in mouse plasma. Of note, pre-ß HDL with hapo A-II was not detected when and mice were fasted overnight.

View larger version (79K): [in this window] [in a new window]   Figure 2. Two-dimensional gel electrophoresis of plasma. Whole plasma from control, hAIItg-, and hAIItg- mice (5 µL), either fed ad libitum or fasted overnight, was subjected to 2D gel electrophoresis, as described in Methods. Lipoproteins from control mice were probed with a rabbit antiserum directed against mapo A-I and lipoproteins from transgenic mice with a rabbit antiserum directed against hapo A-II.

Absence of Atherosclerotic Lesions in Transgenic Mice
Aortic sections from chow-fed control mice (not shown) and hapo A-II high-expressing mice stained with oil red O were totally devoid of lipid infiltrations (Figure II, which can be accessed online at http://atvb.ahajournals.org). "En face" specimens of the thoracic aorta from chow-fed control and high-expressing mice were stained with oil red O and were also totally devoid of lipid infiltrations (data not shown).

	Discussion

Top Abstract Introduction Methods Results Discussion References

 
The present study shows for the first time opposite effects of plasma from mice overexpressing hapo A-II on SR-BI–mediated and ABCA1-mediated cholesterol efflux. The lower cholesterol efflux from SR-BI–expressing Fu5AH cells to plasma from hAIItg mice can be attributed to their decreased plasma HDL level, whereas the greater cholesterol efflux from ABCA1-expressing J774 macrophages may result from the high content of hapo A-II, probably in the form of pre-ß HDL.

In the Fu5AH system, cholesterol efflux correlates best with HDL-PL.^15,16 The markedly reduced cholesterol efflux capacity of plasma from hAIItg mice is consistent with the major decrease in HDL.^12,13 Plasma from independently established mice overexpressing hapo A-II has also displayed lower HDL-PL concentrations and a reduced ability to efflux cholesterol from fibroblasts.¹⁹ The lower efflux capacity of HDL from hAIItg mice compared with HDL from control mice may be attributed to their high hapo A-II content. Indeed, cholesterol efflux from Fu5AH cells to human HDL₃ was negatively correlated with their apoA-II/apoA-I+apoA-II ratio.²⁰ Our results are also in accordance with the lower cholesterol efflux capacity from Fu5AH cells of HDL from hapo A-I/hapo A-II transgenic mice compared with HDL from hapo A-I transgenic mice.²¹ Furthermore, we have demonstrated by use of a large number of human serum samples that LpA-I is a better acceptor than LpA-I/A-II of cholesterol effluxing from Fu5AH cells.¹⁴

Hapo A-I and hapo A-II bind to rodent SR-BI,²² and this binding is essential for cholesterol efflux.²³ However, although apoA-II–enriched HDLs bind to human SR-BI with higher affinity than apoA-I–rich HDLs, they display a lower capacity to deliver cholesteryl esters to human adrenal cells.²⁴ By analogy, the lower efflux capacity of hapo A-II–rich HDL from our hAIItg mice may indicate that hapo A-II is a negative modulator of SR-BI–mediated cholesterol efflux. This negative effect of hapo A-II may be related to the altered cholesterol distribution in plasma membrane domains induced by SR-BI.²⁵

Apart from the greater apoA-II/apoA-I ratio, some of the other HDL modifications of our transgenic mice may contribute to their lower efflux capacities from Fu5AH cells. It is unlikely that the smaller particle size explains their reduced efflux effectiveness, inasmuch as smaller particles, at a given PL concentration, more efficiently remove cellular cholesterol.²⁶ However, the triglyceride enrichment of HDL may affect cholesterol efflux because, at a given PL concentration, triglyceride-enriched HDLs isolated from hypertriglyceridemic subjects were less efficient in extracting cholesterol.²⁷

The major finding of the present study was that cAMP treatment of J774 cells, which upregulates ABCA1,^10,11 markedly increased cholesterol efflux to the plasma of hAIItg mice, in a manner directly proportional to the plasma concentration of hapo A-II; conversely, no variation in efflux to the plasma of control mice was observed. Exposure of macrophages to cAMP stimulated the release of cholesterol and PL to lipid-free apoE,¹⁸ apoA-I, ¹⁷ and apoA-IV.⁹ Our hapo A-II transgenic mice have small amounts of apoE and apoA-IV, which are comparable to those of control mice, whereas HDL and apoA-I are greatly decreased.^12,13 On the other hand, plasma from hAIItg mice contains small-sized HDLs rich in hapo A-II as well as pre-ß HDLs with hapo A-II.¹³ The greater cAMP stimulation of efflux to plasma from fed relative to fasted mice may be linked to the appreciable amount of hapo A-II–containing pre-ß HDLs in the fed animals. Moreover, in the present study, free hapo A-II stimulated cholesterol efflux to the same extent as did free hapo A-I. Accordingly, similar efflux stimulations were reported for unassociated apoA-II and apoA-I from human fibroblasts that express ABCA1,²⁸ whereas expression of ABCA1 in Hela cells markedly increased specific binding of apoA-I and apoA-II to a common binding site.²⁹ Therefore, the greater efflux ability of plasma from hapo A-II transgenic mice may be attributed to the pre-ß HDLs containing hapo A-II and/or to the high total hapo A-II content.

Studies of cholesterol efflux from cultured cells ultimately aim to assess the efficacy of the first step of RCT as a predictor of atherogenic risk.² Thus, it is of interest to compare the results on cholesterol efflux elicited by plasma from various types of mice overexpressing hapo A-II with the degree of aortic lesions developed by the corresponding mice.

Transgenic mice with a high hapo A-II expression did not develop lesions when they were fed a chow diet,³⁰ whereas their plasma displayed a 40% lower efflux capacity from fibroblasts than did plasma from chow-fed control C57BL/6 mice.¹⁹ Conversely, plasma from hapo A-II transgenic and control mice fed the atherogenic diet had similar efflux capacities,¹⁹ although the former developed more aortic lesions than did the latter.³⁰ Independently, established transgenic mice with a moderate expression of hapo A-II developed less aortic lesions on a cholesterol-rich diet than did control mice, although their plasma elicited less cholesterol efflux from Fu5AH cells.³¹ On the other hand, apoA-I knockout (AI-KO) mice have very low plasma HDL levels but are not at increased risk of aortic lesion development, even after administration of the atherogenic diet.³² Chiesa et al³³ expressed hapo A-I, hapo A-II, and both hapo A-I and A-II in the AI-KO background, and they measured cholesterol efflux from Fu5AH cells. Efflux was equally low in plasma from AI-KO and AI-KO/hAIItg mice, whereas it increased appreciably in plasma from AI-KO/hAItg mice, with or without the concomitant expression of hapo A-II. In the present study, the hypertriglyceridemic high-expressing mice did not develop atherosclerotic lesions, although their HDL and plasma displayed lower efflux capacities from Fu5AH cells than did HDL and plasma from control mice.

Taken together, the results of the above studies clearly show that variations in the ability of plasma and HDL to induce cholesterol efflux from Fu5AH cells is not predictive of aortic lesion development of the corresponding mice. To what extent SR-BI–expressing cells display appreciable cholesterol efflux in vivo has not been established at present. Conversely, it is well known that SR-BI mediates selective uptake of cholesteryl esters in steroidogenic tissues and the liver.³⁴ Because SR-BI is equally efficient at mediating the import and export of cholesterol to and from cells to lipoproteins and other acceptors,^7,8 the specific metabolic conditions in vivo favoring cholesterol influx or efflux remain to be established.

By contrast, expression of a nonfunctional ABCA1 protein leads to increased atherosclerotic risk in patients with Tangier disease,³⁵ whereas the expression of a partially functional ABCA1 is correlated with HDL deficiency in humans.^2,36 In this case, lack of cholesterol efflux is correlated with greater atherosclerotic risk, thus providing evidence that strengthens the link between HDL, RCT, and atherosclerosis.³⁵ Plasma from our hAIItg mice markedly stimulated cholesterol efflux from J774 macrophages pretreated with cAMP, which upregulates ABCA1 expression,^10,11 whereas the coronary arteries of hAIItg mice were totally devoid of lipid infiltrations.

In conclusion, our data demonstrate opposite effects of plasma from hapo A-II transgenic mice on cholesterol efflux from Fu5AH hepatoma cells and from J774 macrophages. Because macrophages are implicated in the early steps of atherogenesis, the increased ability of plasma with a high hapo A-II content to extract cholesterol from such cells indicates an antiatherogenic influence of hapo A-II.

	Acknowledgments

 
We thank Sophie Goyer, Mai N’Guyen, Carole Lasne, and Maryse Séau for excellent technical assistance and Nhuan Quang Tran for help with the graphics. We are very grateful to George Rothblat for his fruitful help and discussions.

Received November 27, 2001; accepted January 30, 2002.

	References

Top Abstract Introduction Methods Results Discussion References

 

1. Fielding CJ, Fielding PE. Molecular physiology of reverse cholesterol transport. J Lipid Res. 1995; 36: 211–228.
2. Tall A, Wang N. Tangier disease as a test of the reverse cholesterol transport hypothesis. J Clin Invest. 2000; 106: 1205–1207.
3. Rothblat GH, de la Llera Moya M, Atger V, Kellner-Weibel G, Williams DL, Phillips MC. Cell cholesterol efflux: integration of old and new observations provides new insights. J Lipid Res. 1999; 40: 781–796.
4. Huang H, von Eckardstein A, Wu S, Assmann G. Cholesterol efflux, cholesterol esterification and cholesteryl ester transfer by Lp AI and Lp AI:AII in native plasma. Arterioscler Thromb Vasc Biol. 1995; 15: 1412–1418.
5. Oikawa S, Mendez AJ, Oram JF, Bierman EL, Cheung MC. Effects of high density lipoprotein particles containing apo AI, with or without apo II, on intracellular cholesterol efflux. Biochim Biophys Acta. 1993; 1165: 327–334.
6. Yancey PG, de la Llera Moya M, Swarnakar S, Monzo P, Klein SM, Connelly MA, Johnson WJ, Williams DL, Rothblat GH. High density lipoprotein phospholipid composition is a major determinant of the bi-directional flux and net movement of cellular free cholesterol mediated by scavenger receptor BI. J Biol Chem. 2000; 275: 36596–36604.
7. Ji Y, Jian B, Wang N, Sun Y, de la Llera Moya M, Phillips MC, Rothblat GH, Swaney JB, Tall A. Scavenger receptor BI promotes high density lipoprotein mediated cellular cholesterol efflux. J Biol Chem. 1997; 272: 20982–20985.
8. Stangl H, Cao G, Wyne KL, Hobbs HH. Scavenger receptor, class B, type I-dependent stimulation of cholesterol esterification by high density lipoproteins, low density lipoproteins, and nonlipoprotein cholesterol. J Biol Chem. 1998; 273: 31002–31008.
9. Fournier N, Atger V, Paul JL, Sturm M, Duverger N, Rothblat GH, Moatti N. Human apo AIV overexpression in transgenic mice induces cAMP stimulated cholesterol efflux from J774 macrophages to whole serum. Arterioscler Thromb Vasc Biol. 2000; 20: 1283–1292.
10. Bortnick AE, Rothblat GH, Stoudt G, Hoppe KL, Royer LJ, McNeish J, Francone OL. The correlation of ATP-binding cassette 1 mRNA levels with cholesterol efflux from various cell lines. J Biol Chem. 2000; 275: 28634–28640.
11. 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.
12. Boisfer E, Lambert G, Atger V, Tran NQ, Pastier D, Benetello C, Trottier JF, Beaucamps I, Antonucci M, Laplaud M, et al. Overexpression of human apolipoprotein AII in mice induces hypertriglyceridemia due to defective very low density lipoprotein hydrolysis. J Biol Chem. 1999; 274: 11564–11572.
13. Pastier D, Dugué S, Boisfer E, Atger V, Tran NQ, van Tol A, Chapman MJ, Chambaz J, Laplaud PM, Kalopissis AD. Apolipoprotein A-II:A-I ratio is a key determinant in vivo of HDL concentration and formation of pre-ß HDL containing apolipoprotein A-II. Biochemistry. 2001; 40: 12243–12253.
14. de la Llera Moya M, Atger V, Paul JL, Fournier N, Moatti N, Giral P, Friday KE, Rothblat GH. A cell culture system for screening human serum for ability to promote cellular cholesterol efflux: relationships between serum components and efflux, esterification and transfer. Arterioscler Thromb. 1994; 14: 1056–1065.
15. Fournier N, de la Llera Moya M, Burkey B, Swaney J, Paterniti JJ, Moatti N, Atger V, Rothblat GH. The role of HDL phospholipids in efflux of cell cholesterol to whole serum: studies with human apo AI transgenic rats. J Lipid Res. 1996; 37: 1704–1711.
16. Fournier N, Paul JL, Atger V, Cogny A, Soni T, de la Llera Moya M, Rothblat G, Moatti N. HDL phospholipid content and composition as a major factor determining cholesterol efflux capacity from Fu5AH cells to human serum. Arterioscler Thromb Vasc Biol. 1997; 17: 2685–2691.
17. Sakr SW, Stoudt GW, Williams D, Phillips MC, Rothblat GH. Induction of cellular cholesterol efflux to lipid-free apolipoprotein AI by cAMP. Biochim Biophys Acta. 1999; 1438: 85–98.
18. Smith JD, Miyata M, Ginsberg M, Grigaux C, Shmookler E, Plump AS. Cyclic AMP induces apolipoprotein E binding activity and promotes cholesterol efflux from a macrophage cell line to apolipoprotein acceptors. J Biol Chem. 1996; 271: 30647–30655.
19. Julve-Gil J, Ruiz-Perez E, Casaroli-Marano RP, Marzal-Casacuberta A, Escola-Gil JC, Gonzales-Sastre F, Blanco-Vaca F. Free cholesterol deposition in the cornea of human apolipoprotein A-II transgenic mice with functional lecithin:cholesterol acyltransferase deficiency. Metabolism. 1999; 48: 415–421.
20. Lagrost L, Dengremont C, Athias A, de Geitere C, Fruchart JC, Lallemant C, Gambert P, Castro G. Modulation of cholesterol efflux from Fu5AH hepatoma cells by the apolipoprotein content of high density lipoprotein particles. J Biol Chem. 1995; 270: 13004–13009.
21. Castro G, Parmentier Nihoul L, Dengremont C, de Geitere C, Delfly B, Tailleux A, Fievet C, Duverger N, Denefle P, Fruchart JC, et al. Cholesterol efflux, lecithin-cholesterol acyltransferase activity, and pre-ß particle formation by serum from human apolipoprotein A-I and apolipoprotein A-I/apolipoprotein A-II transgenic mice consistent with the latter being less effective for reverse cholesterol transport. Biochemistry. 1997; 36: 2243–2249.
22. Xu SZ, Laccotripe M, Huang XW, Rigotti A, Zannis VI, Krieger M. Apolipoproteins of HDL can directly mediate binding to the scavenger receptor SR-BI, an HDL receptor that mediates selective lipid uptake. J Lipid Res. 1997; 38: 1289–1298.
23. Gu X, Kozarsky K, Krieger M. Scavenger receptor class B, type I-mediated. J Biol Chem. 2000; 275: 29993–30001.
24. Pilon A, Briand O, Lestavel S, Copin C, Majd Z, Fruchart JC, Castro G, Clavey V. Apolipoprotein AII enrichment of HDL enhances their affinity for class B type I scavenger receptor but inhibits specific cholesteryl ester uptake. Arterioscler Thromb Vasc Biol. 2000; 20: 1074–1081.
25. Kellner-Weibel G, de la Llera Moya M, Connelly MA, Stoudt G, Christian AE, Haynes MP, Williams DL, Rothblat GH. Expression of scavenger receptor BI in COS-7 cells alters cholesterol content and distribution. Biochemistry. 2000; 39: 221–229.
26. Davidson WS, Rodrigueza WV, Lund-Katz S, Johnson WJ, Rothblat GH, Phillips MC. Effects of acceptor particle size on the efflux of cellular free cholesterol. J Biol Chem. 1995; 270: 17106–17113.
27. Brites FD, Bonavita CD, De Geitere C, Cloes M, Delfly B, Yael MJ, Fruchart JC, Wikinski RW, Castro GR. Alterations in the main steps of reverse cholesterol transport in male patients with primary hypertriglyceridemia and low HDL-cholesterol levels. Atherosclerosis. 2000; 152: 181–192.
28. Remaley AT, Schumacher UK, Stonik JA, Farsi BD, Nazih H, Brewer HB. Decreased reverse cholesterol transport from Tangier disease fibroblasts: acceptor specificity and effect of brefeldin on lipid efflux. Arterioscler Thromb Vasc Biol. 1997; 17: 1813–1821.
29. Remaley AT, Stonik JA, Demosky SJ, Neufeld EB, Bocharov AV, Vishnyakova TG, Eggerman TL, Patterson AP, Duverger N, Santamarina-Fojo S, et al. Apolipoprotein specificity for lipid efflux by the human ABCA1 transporter. Biochem Biophys Res Commun. 2001; 280: 818–823.
30. Escola-Gil JC, Marzal-Casacuberta A, Julve-Gil J, Ishida BY, Ordonez-Llanos J, Chan L, Gonzalez-Sastre F, Blanco-Vaca F. Human apolipoprotein A-II is a proatherogenic molecule when it is expressed in transgenic mice at a level similar to that in humans: evidence of a potentially relevant species-specific interaction with diet. J Lipid Res. 1998; 39: 457–462.
31. Tailleux A, Bouly M, Luc G, Castro G, Caillaud JM, Hennuyer N, Poulain P, Fruchart JC, Duverger N, Fiévet C. Decreased susceptibility to diet-induced atherosclerosis in human apolipoprotein A-II transgenic mice. Arterioscler Thromb Vasc Biol. 2000; 20: 2453–2458.
32. Li H, Reddick RL, Maeda N. Lack of apoAI is not associated with increased susceptibility to atherosclerosis in mice. Arterioscler Thromb. 1993; 13: 1814–1821.
33. Chiesa G, Parolini C, Canavesi M, Colombo N, Sirtori CR, Fumagalli R, Franceschini G, Bernini F. Human apolipoproteins AI and AII in cell cholesterol efflux: studies with transgenic mice. Arterioscler Thromb Vasc Biol. 1998; 18: 1417–1423.
34. Krieger M, Kozarsky K. Influence of the HDL receptor SR-BI on atherosclerosis. Curr Opin Lipidol. 1999; 10: 491–497.
35. Hayden MR, Clee SM, Brooks-Wilson A, Genest J, Attie A, Kastelein JJ. Cholesterol efflux regulatory protein, Tangier disease and familial high-density lipoprotein deficiency. Curr Opin Lipidol. 2000; 11: 117–122.
36. Clee SM, Kastelein JJ, van Dam M, Marcil M, Roomp K, Zwarts KY, Collins JA, Roelants R, Tamasawa N, Stulc T, et al. Age and residual cholesterol efflux affect HDL cholesterol levels and coronary artery disease in ABCA1 heterozygotes. J Clin Invest. 2000; 106: 1263–1270.

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				N. Rotllan, V. Ribas, L. Calpe-Berdiel, J. M. Martin-Campos, F. Blanco-Vaca, and J. C. Escola-Gil Overexpression of Human Apolipoprotein A-II in Transgenic Mice Does Not Impair Macrophage-Specific Reverse Cholesterol Transport In Vivo Arterioscler. Thromb. Vasc. Biol., September 1, 2005; 25(9): e128 - e132. [Abstract] [Full Text] [PDF]

				J. W. J. Beulens, A. Sierksma, A. van Tol, N. Fournier, T. van Gent, J-L. Paul, and H. F. J. Hendriks Moderate alcohol consumption increases cholesterol efflux mediated by ABCA1 J. Lipid Res., September 1, 2004; 45(9): 1716 - 1723. [Abstract] [Full Text] [PDF]

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