Structural and functional properties of human plasma high density-sized lipoprotein containing only apoE particles

To investigate the metabolism of HDL-apolipoprotein E (apoE) particles in human plasma, we isolated a fraction of plasma HDL-apoEs that lack apoA-I (HDL-LpE) from subjects with apoE3/3 phenotype by immunoaffinity. Plasma HDL-LpE had a particle size ranging from 9 nm to 18.5 nm in diameter and was characterized by two-dimensional nondenaturing gradient gel electrophoresis as having either γ-, preβ1-, preβ2-, or α-electrophoretic mobility. HDL-LpE was also present in the medium of cultured human hepatoma cell lines and monocyte-derived macrophages. The majority of apoE3 was found as a monomeric form in HDL-LpE and floated at density d > 1.21 g/ml. Plasma levels of HDL-LpE in normolipidemic, CETP-deficient, and ABCA1-deficient subjects were 0.72 ± 0.15 mg/dl (n = 12), 1.77 ± 0.75 mg/dl (n = 3), and 0.55 ± 0.11 mg/dl (n = 3), respectively. The ratio of HDL-apoE containing apoA-I to HDL-LpE was significantly higher 4 h after a fat load, representing a 35 ± 9% increase (n = 3). Isolated plasma HDL-LpE3 was as effective as apoE3, reconstituted HDL particles, or apoA-I in promoting cellular cholesterol efflux.These results demonstrate that 1) plasma HDL-LpE may have hepatogenous and macrophagic origins; 2) HDL-LpE was preserved even with large reductions in apoA-I-containing lipoproteins; 3) HDL-LpE was active in the transfer of apoE to triglyceride-rich lipoproteins, and 4) HDL-LpEs efficiently take up cell-derived cholesterol. To investigate the metabolism of HDL-apolipoprotein E (apoE) particles in human plasma, we isolated a fraction of plasma HDL-apoEs that lack apoA-I (HDL-LpE) from subjects with apoE3/3 phenotype by immunoaffinity. Plasma HDL-LpE had a particle size ranging from 9 nm to 18.5 nm in diameter and was characterized by two-dimensional nondenaturing gradient gel electrophoresis as having either γ-, preβ1-, preβ2-, or α-electrophoretic mobility. HDL-LpE was also present in the medium of cultured human hepatoma cell lines and monocyte-derived macrophages. The majority of apoE3 was found as a monomeric form in HDL-LpE and floated at density d > 1.21 g/ml. Plasma levels of HDL-LpE in normolipidemic, CETP-deficient, and ABCA1-deficient subjects were 0.72 ± 0.15 mg/dl (n = 12), 1.77 ± 0.75 mg/dl (n = 3), and 0.55 ± 0.11 mg/dl (n = 3), respectively. The ratio of HDL-apoE containing apoA-I to HDL-LpE was significantly higher 4 h after a fat load, representing a 35 ± 9% increase (n = 3). Isolated plasma HDL-LpE3 was as effective as apoE3, reconstituted HDL particles, or apoA-I in promoting cellular cholesterol efflux. These results demonstrate that 1) plasma HDL-LpE may have hepatogenous and macrophagic origins; 2) HDL-LpE was preserved even with large reductions in apoA-I-containing lipoproteins; 3) HDL-LpE was active in the transfer of apoE to triglyceride-rich lipoproteins, and 4) HDL-LpEs efficiently take up cell-derived cholesterol. The importance of apolipoprotein E (apoE), a multifunctional protein, in the onset and development of atherosclerosis and in the pathophysiology of Alzheimer's disease, has been recognized for a number of years. Increasing evidence from both animal and human studies suggests that apoE is able to protect against atherosclerosis by a) promoting efficient uptake of triglyceride-rich lipoproteins (TRLs) from the circulation (1Mahley R.W. Apolipoprotein E: cholesterol transport protein with expanding role in cell biology.Science. 1988; 240: 622-630Google Scholar), b) maintaining normal macrophage lipid homeostasis (2Brown M.S. Goldstein J.L. Lipoprotein metabolism in the macrophage: implications for cholesterol deposition in atherosclerosis.Annu. Rev. Biochem. 1983; 52: 223-261Google Scholar), c) playing a role in cellular cholesterol efflux and reverse cholesterol transport (RCT) (3Tall A.R. Plasma high density lipoproteins. Metabolism and relationship to atherogenesis.J. Clin. Invest. 1990; 86: 379-384Google Scholar), d) preventing oxidation (4Parthasarathy S. Barnett J. Fong L.G. High-density lipoprotein inhibits the oxidative modification of low-density lipoprotein.Biochim. Biophys. Acta. 1990; 1044: 275-283Google Scholar), e) modulating inflammatory response by suppressing lymphocyte activation (5Hui D.Y. Harmony J.A. Innerarity T.L. Mahley R.W. Immunoregulatory plasma lipoproteins. Role of apoprotein E and apoprotein B.J. Biol. Chem. 1980; 255: 11775-11781Google Scholar), and f) restricting platelet aggregation (6Riddell D.R. Graham A. Owen J.S. Apolipoprotein E inhibits platelet aggregation through the L-arginine:nitric oxide pathway. Implications for vascular disease.J. Biol. Chem. 1997; 272: 89-95Google Scholar) and suppressing growth factor-induced smooth muscle cell migration and proliferation (7Ishigami M. Swertfeger D.K. Granholm N.A. Hui D.Y. Apolipoprotein E inhibits platelet-derived growth factor-induced vascular smooth muscle cell migration and proliferation by suppressing signal transduction and preventing cell entry to G1 phase.J. Biol. Chem. 1998; 273: 20156-20161Google Scholar). ApoE is believed to play a significant role in the pathophysiology of Alzheimer's disease by controlling neuronal growth (8Nathan B.P. Bellosta S. Sanan D.A. Weisgraber K.H. Mahley R.W. Pitas R.E. Differential effects of apolipoproteins E3 and E4 on neuronal growth in vitro.Science. 1994; 264: 850-852Google Scholar). Importantly, both immunosuppression and stimulation of neurite outgrowth by apoE are unrelated to its cholesterol-transporting properties because minimally lipidated or delipidated apoEs are equally active in regulating these lymphocyte and neuronal cell functions (9DeMattos R.B. Curtiss L.K. Williams D.L. A minimally lipidated form of cell-derived apolipoprotein E exhibits isoform-specific stimulation of neurite outgrowth in the absence of exogenous lipids or lipoproteins.J. Biol. Chem. 1998; 273: 4206-4212Google Scholar). In contrast, apoE inhibition of platelet aggregation requires its presence in a lipoprotein form (6Riddell D.R. Graham A. Owen J.S. Apolipoprotein E inhibits platelet aggregation through the L-arginine:nitric oxide pathway. Implications for vascular disease.J. Biol. Chem. 1997; 272: 89-95Google Scholar). Taken together, these studies suggest that minimally lipidated or delipidated apoE in circulation may have a direct impact on vascular occlusive diseases independent of its cholesterol transport function. In human plasma, apoE is almost entirely associated with lipoproteins containing apoB or apoA-I (10Castro G.R. Fielding C.J. Evidence for the distribution of apolipoprotein E between lipoprotein classes in human normocholesterolemic plasma and for the origin of unassociated apolipoprotein E (Lp-E).J. Lipid Res. 1984; 25: 58-67Google Scholar), though several studies have demonstrated the existence of minor lipoprotein subfractions similar in size to HDL and containing apoE as their only protein component (11Huang Y. von Eckardstein A. Wu S. Maeda N. Assmann G. A plasma lipoprotein containing only apolipoprotein E and with gamma mobility on electrophoresis releases cholesterol from cells.Proc. Natl. Acad. Sci. USA. 1994; 91: 1834-1838Google Scholar, 12Krimbou L. Tremblay M. Davignon J. Cohn J.S. Characterization of human plasma apolipoprotein E-containing lipoproteins in the high density lipoprotein size range: focus on pre- beta1-LpE, pre-beta2-LpE, and alpha-LpE.J. Lipid Res. 1997; 38: 35-48Google Scholar, 13Krimbou L. Tremblay M. Jacques H. Davignon J. Cohn J.S. In vitro factors affecting the concentration of gamma-LpE (gamma-LpE) in human plasma.J. Lipid Res. 1998; 39: 861-872Google Scholar). It has been suggested that HDL-apoE is involved in several aspects of plasma lipoprotein metabolism, including 1) receptor-mediated delivery of HDL cholesterol to the liver (14Mahley R.W. Innerarity T.L. Weisgraber K.B. Oh S.Y. Altered metabolism (in vivo and in vitro) of plasma lipoproteins after selective chemical modification of lysine residues of the apoproteins.J. Clin. Invest. 1979; 64: 743-750Google Scholar), 2) hepatic lipase-catalyzed hydrolysis of HDL phospholipid (15Thuren T. Weisgraber K.H. Sisson P. Waite M. Role of apolipoprotein E in hepatic lipase catalyzed hydrolysis of phospholipid in high-density lipoproteins.Biochemistry. 1992; 31: 2332-2338Google Scholar), 3) plasma cholesterol esterification (16Zorich N. Jonas A. Pownall H.J. Activation of lecithin cholesterol acyltransferase by human apolipoprotein E in discoidal complexes with lipids.J. Biol. Chem. 1985; 260: 8831-8837Google Scholar), 4) plasma cholesteryl ester (CE) transfer (17Yamashita S. Sprecher D.L. Sakai N. Matsuzawa Y. Tarui S. Hui D.Y. Accumulation of apolipoprotein E-rich high density lipoproteins in hyperalphalipoproteinemic human subjects with plasma cholesteryl ester transfer protein deficiency.J. Clin. Invest. 1990; 86: 688-695Google Scholar), 5) efflux of cell-derived cholesterol (11Huang Y. von Eckardstein A. Wu S. Maeda N. Assmann G. A plasma lipoprotein containing only apolipoprotein E and with gamma mobility on electrophoresis releases cholesterol from cells.Proc. Natl. Acad. Sci. USA. 1994; 91: 1834-1838Google Scholar, 18Huang Y. von Eckardstein A. Wu S. Assmann G. Effects of the apolipoprotein E polymorphism on uptake and transfer of cell-derived cholesterol in plasma.J. Clin. Invest. 1995; 96: 2693-2701Google Scholar), and 6) stimulation of endothelial production of heparin sulfate (19Paka L. Kako Y. Obunike J.C. Pillarisetti S. Apolipoprotein E containing high density lipoprotein stimulates endothelial production of heparan sulfate rich in biologically active heparin-like domains. A potential mechanism for the anti-atherogenic actions of vascular apolipoprotein e.J. Biol. Chem. 1999; 274: 4816-4823Google Scholar). The present study aims to provide evidence for the physiological presence of HDL-lipoprotein containing only apoE (LpE) in human plasma and the role of these particles in the RCT process. Our results demonstrated the presence of different-sized HDL containing only apoE particles in normolipidemic and hypoalphalipoproteinemic human plasma. HDL-LpE particles participate in a dynamic traffic of apoE between HDL and TRLs and were efficient acceptors of cell-derived cholesterol. Blood samples were obtained from and subjects with apoE3/3 phenotype after Blood was from the containing were in Plasma was from by and was in of HDL and of particles by or study was by the of the Plasma from with cholesteryl ester transfer protein was by from of plasma from subjects with disease and apoA-I was by von Eckardstein from the of A. L. A. J. H. H. Eckardstein A. Assmann G. for a apolipoprotein and apolipoprotein in with absence of HDL and and plasma from subjects with HDL was from and was M. A. L. J.A. M. S. M. S. J. in the in HDL with cholesterol 1999; Scholar, M. L. L. Cohn J.S. J. cholesterol transport and efflux in are in subjects with HDL Biol. 1999; Scholar). Plasma was of lipoprotein by with as H. H. Hui Y. H. H. H. M. and in high density lipoprotein in with of cholesteryl ester transfer protein deficiency.J. Lipid Res. 1997; 38: Scholar). the plasma was with of and the was to for at HDL was in HDL-LpE were isolated from plasma of lipoproteins to the of apoB was to of gel of apoA-I and to Tremblay M. A. Jacques H. L. Davignon J. Cohn J.S. Plasma particle lipid and apolipoprotein levels in normolipidemic and 1998; Scholar). The was for h at with a The was to for The containing HDL-LpE was and at of The of apoE after of and apoA-I-containing lipoproteins by and in normolipidemic subjects with apoE3/3 phenotype was ± (n = the human and and was as (9DeMattos R.B. Curtiss L.K. Williams D.L. A minimally lipidated form of cell-derived apolipoprotein E exhibits isoform-specific stimulation of neurite outgrowth in the absence of exogenous lipids or lipoproteins.J. Biol. Chem. 1998; 273: 4206-4212Google Scholar). plasma from a normolipidemic with apoE3/3 phenotype was of lipoprotein by with HDL was of apoA-I-containing lipoproteins by and HDL-LpE particles were isolated by isolated plasma HDL-LpE3 particles were for cellular cholesterol efflux Plasma was of lipoprotein by with and apoA-I-containing particles were by as we have Tremblay M. L. Davignon J. J. Cohn J.S. HDL characterized by of Biol. 1998; Scholar). plasma of apoB was to of for at and at for The was with and apoA-I-containing particles were in and with (9DeMattos R.B. Curtiss L.K. Williams D.L. A minimally lipidated form of cell-derived apolipoprotein E exhibits isoform-specific stimulation of neurite outgrowth in the absence of exogenous lipids or lipoproteins.J. Biol. Chem. 1998; 273: 4206-4212Google Scholar). The apoA-I-containing particles were and Isolated HDL-apoE with apoA-I particles were for of apoE The concentration of HDL-apoEs with apoA-I was as the between HDL-apoE and both by Lipoprotein in the HDL size in plasma and HDL-LpE were by two-dimensional nondenaturing gradient gel electrophoresis as L. Tremblay M. Davignon J. Cohn J.S. Characterization of human plasma apolipoprotein E-containing lipoproteins in the high density lipoprotein size range: focus on pre- beta1-LpE, pre-beta2-LpE, and alpha-LpE.J. Lipid Res. 1997; 38: 35-48Google Scholar, L. M. Davignon J. J. of acyltransferase with density lipoprotein protein Evidence for receptor-mediated in Biol. Chem. Scholar). plasma samples and HDL-LpE from of the were in the to their by gel electrophoresis and in the to the by or gradient gel electrophoresis A protein nm to of and a Biochem. Scholar) was as a on and lipoproteins were and apoE or apoA-I-containing lipoproteins were by the with apoE or with The presence of was by hepatoma cell lines were cultured as we have L. M. Davignon J. J. of acyltransferase with density lipoprotein protein Evidence for receptor-mediated in Biol. Chem. Scholar). were in medium with and a h medium from was in the presence of by to a of and by of human monocyte-derived was as of high density lipoproteins by human monocyte-derived is a mechanism that to macrophage cholesterol Biol. Chem. 1994; Scholar). were obtained by from a normolipidemic with apoE3/3 were 35 diameter and for h at to the to was with of to and with of containing a h medium from was and by and were on concentration was by cholesterol in the after of lipoproteins with from the d > fraction by Plasma apoA-I and apoB were by or by ApoE were by of plasma by electrophoresis J.S. of apolipoprotein E: to Chem. 1990; Scholar). ApoE in plasma, and HDL-LpE were by Plasma fraction d > 1.21 mg/dl was isolated from normolipidemic plasma by a HDL containing only apoE particles were as A. A. L. The number of of apolipoproteins and the size and properties of their reconstituted lipoprotein Biol. Chem. Scholar). was by with Goldstein J.L. M.S. of density lipoprotein and of cholesterol metabolism in Natl. Acad. Sci. USA. Scholar) and with as M. S. T. H. uptake of low-density cholesteryl by human human hepatoma and in Biophys. Acta. 1995; Scholar). was from to by by transfer of the from to were from by density The of the was of were with were as ± was for between In to the relationship of HDL-apoE particles with lipoproteins containing plasma was of lipoproteins by with and of apoA-I-containing lipoproteins by as in and of isolated plasma HDL-LpE fraction from a normolipidemic is in The majority of HDL-LpE had a particle size from 9 nm to 18.5 nm in and characterized as having either γ-, preβ1-, or α-electrophoretic mobility. HDL-LpE as and to their migration in the HDL-LpE or with or as by by with have that the presence of HDL-LpE after is of the presence of in vivo L. Tremblay M. Davignon J. Cohn J.S. Characterization of human plasma apolipoprotein E-containing lipoproteins in the high density lipoprotein size range: focus on pre- beta1-LpE, pre-beta2-LpE, and alpha-LpE.J. Lipid Res. 1997; 38: 35-48Google Scholar, 13Krimbou L. Tremblay M. Jacques H. Davignon J. Cohn J.S. In vitro factors affecting the concentration of gamma-LpE (gamma-LpE) in human plasma.J. Lipid Res. 1998; 39: 861-872Google Scholar). The was HDL-LpE particles were by or were a of plasma lipoproteins was in HDL-LpE was isolated from the medium of cultured and monocyte-derived macrophages. The medium of cultured was of lipoprotein by with and of apoA-I-containing lipoproteins by in lipoprotein apoA-I in the HDL size with a particle diameter ranging from nm to 18.5 and had mobility on the of lipoproteins from cultured monocyte-derived from a normolipidemic with apoE3/3 phenotype by that a significant of particles by human have mobility and particle size ranging from nm to 18.5 the majority of particles by were in the d > 1.21 g/ml. contrast, cholesterol of large particles with a density similar to HDL and particles The of apoE HDL-apoE was by by with apoE as in The of apoE3 were found in HDL-apoE In to the monomeric apoE3 both and were present in HDL-apoE with apoA-I isolated by as in and of the apoE3 was found as a monomeric form in HDL-LpE To density distribution and of HDL-LpE particles, isolated HDL-LpE to demonstrated that of the HDL-LpE was in the fraction of the density gradient > as in apoE was in the density d 1.21 Plasma apoE and apoA-I > were as in as in particles in d > 1.21 are similar to found in HDL-LpE > particles were also in the fraction of the density gradient > In to the plasma concentration of HDL-LpE was on plasma HDL HDL-LpE was in plasma from subjects and ABCA1-deficient in the concentration of HDL-LpE was significantly higher in 1.77 ± 0.75 mg/dl (n = 3), with normal 0.72 ± 0.15 mg/dl (n = in ABCA1-deficient the or absence apoA-I-containing HDL particles HDL and the of plasma HDL-LpE was preserved 0.55 ± 0.11 mg/dl (n = 3) HDL-apoE was also found in of and apoA-I of and plasma HDL-lipoprotein containing only apoE in normolipidemic, cholesteryl ester transfer protein and subjects with apoE3/3 of HDL-apoE (n = ± ± ± ± ± ± ± ± ± ± HDL ± ± cholesteryl ester transfer lipoprotein containing only of HDL-apoE in a cholesteryl ester transfer lipoprotein containing only It is that the distribution of apoE between plasma lipoproteins after the of a L. Tremblay M. Davignon J. Cohn J.S. Characterization of human plasma apolipoprotein E-containing lipoproteins in the high density lipoprotein size range: focus on pre- beta1-LpE, pre-beta2-LpE, and alpha-LpE.J. Lipid Res. 1997; 38: 35-48Google Scholar, of apolipoprotein E metabolism in Lipid Res. Scholar). In to study HDL-LpE particles in a physiological the plasma apoE concentration in HDL-apoE was in subjects after and at h for 4 h or h after the of fat The of these was to subfractions of HDL were active in apoE plasma for is in in the plasma concentration of apoE was the a of apoE The plasma concentration of HDL-apoE HDL-apoE with and HDL-LpE significantly after the fat and to the levels HDL-LpE particles 4 h after the fat To the importance of HDL-LpE to transfer of apoE the the ratio of HDL-apoE with apoA-I to HDL-LpE was in normolipidemic subjects after fat in ratio was significantly higher 4 h after a fat load, representing a ± increase (n = 3), with the = It is that HDL-apoE particles play role in the RCT process. In to provide direct evidence that HDL-LpE particles as of cellular were with for h and in medium containing of either human plasma apoE3, reconstituted HDL particles isolated plasma HDL-LpE particles from a normolipidemic with apoE3/3 or in isolated plasma HDL-LpE3 particles were as effective as apoE3, or apoA-I in promoting efflux of from macrophages. The results of the present study demonstrate the presence of HDL-LpE in the plasma of normolipidemic HDL-LpE had a particle size ranging from 9 nm to 18.5 nm in and was in size between and HDL-LpE particles were characterized by as having either γ-, preβ1-, preβ2-, or α-electrophoretic mobility and The physiological existence of plasma HDL-LpE particles was by the presence of lipoproteins containing only apoE in the medium of cultured and monocyte-derived that plasma HDL-LpE may have hepatogenous and macrophagic and S. The of apolipoprotein E with apolipoprotein lipoproteins in Biol. 1995; Scholar) had that lipoprotein particles by have and mobility on the has been that cholesterol human apoE with a density g/ml. contrast, cholesterol of the of apoE with phospholipid and cholesterol to form discoidal particles that floated at of Apolipoprotein E by human monocyte-derived cholesterol efflux that in the absence of cholesterol Biol. Chem. Scholar). It was that the majority of apoE3 in the plasma in either as the or as the K.H. of the of apolipoprotein E3 in plasma. on Biol. Chem. Scholar). In we demonstrate that the of apoE3 are present in HDL-apoE of apoE3 was found as a monomeric form in HDL-LpE Weisgraber and K.H. of the of apolipoprotein E3 in plasma. on Biol. Chem. Scholar) had that apoE3 on and was higher the = for a It is that the form of apoE3 apoE3 with plasma In of we have that apoE was found associated with in human plasma L. Tremblay M. Davignon J. Cohn J.S. of apolipoprotein E with in human plasma.J. Lipid Res. 1998; 39: Scholar). In normolipidemic the concentration of HDL-LpE was 0.72 ± 0.15 representing of HDL-apoE studies have the presence of of HDL particles in subjects H. H. Hui Y. H. H. H. M. and in high density lipoprotein in with of cholesteryl ester transfer protein deficiency.J. Lipid Res. 1997; 38: Scholar, H. M. S. S. plasma apolipoprotein E-rich high-density lipoprotein and its on high-density lipoprotein cholesterol in with to cholesteryl ester transfer Biol. Scholar). In the present subjects were found to have a plasma HDL-LpE concentration with normal subjects In of HDL-LpE from subjects was with mobility found that HDL-LpE particles were preserved even with large reductions in apoA-I-containing lipoproteins. is by the that 1) in ABCA1-deficient subjects M. A. L. J.A. M. S. M. S. J. in the in HDL with cholesterol 1999; Scholar, M. L. L. Cohn J.S. J. cholesterol transport and efflux in are in subjects with HDL Biol. 1999; Scholar), the or absence apoA-I-containing HDL particles HDL and the levels of plasma HDL-LpE were preserved ± 0.11 = 3) and 2) HDL-apoE was present in of In we demonstrated that in normal plasma, HDL-apoE participate in the plasma transfer of apoE the L. Tremblay M. Davignon J. Cohn J.S. Characterization of human plasma apolipoprotein E-containing lipoproteins in the high density lipoprotein size range: focus on pre- beta1-LpE, pre-beta2-LpE, and alpha-LpE.J. Lipid Res. 1997; 38: 35-48Google Scholar). in that HDL-apoE has similar in apoE at 4 h after the fat load, we demonstrate that HDL-LpE particles were active in apoE HDL-apoE with apoA-I ± = we that apoE3 in HDL-apoE the transfer of apoE to the the lipid of apoE in HDL-apoE its In the present evidence was in obtained to both of these of apoE3 was found as a monomeric form in HDL-LpE the majority of apoE3 in HDL-apoE with apoA-I as both and the the majority of HDL-LpE was at d > 1.21 that these particles were or lipid of apoE in HDL-apoE its transfer between lipoproteins in the in the that apoE3 its to K.H. of the of apolipoprotein E3 in plasma. on Biol. Chem. Scholar). the monomeric form of apoE the biologically active form of evidence for the importance of HDL-LpE in the transfer of apoE to the of was by the that 1) of apoE associated with lipoproteins is found as monomeric and 2) 4 h after the fat and after the of HDL-LpE concentration to its ± ± and ± and the in vitro of in a significant of HDL-LpE particles, have mobility on gel in size to plasma HDL-LpE with the that in vivo of may HDL-LpE particles L. Tremblay M. Jacques H. Davignon J. Cohn J.S. In vitro factors affecting the concentration of gamma-LpE (gamma-LpE) in human plasma.J. Lipid Res. 1998; 39: 861-872Google Scholar). The by HDL against atherosclerosis are the of with to at for disease G. von Eckardstein A. M. P. of high-density lipoprotein metabolism and reverse cholesterol Scholar, M. L. Davignon J. J. J. HDL in and Biol. 1995; Scholar). the that the of RCT in both and normal plasma on the majority of HDL particles on the presence of effective subfractions involved in the RCT Eckardstein A. Y. Wu S. H. G. Assmann G. cholesterol transport in plasma of with of HDL Biol. 1995; Scholar). is by the that 1) HDL-LpE particles were present in with 4) and 2) isolated plasma HDL-LpE3 particles efficiently take up cell-derived cholesterol a lipoprotein that apoE as its protein component present in has been to play a role in cellular cholesterol efflux by as of cell-derived cholesterol in normal and plasma subjects Eckardstein A. Y. Wu S. H. G. Assmann G. cholesterol transport in plasma of with of HDL Biol. 1995; Scholar). has been that plasma of apoE has a to cholesterol efflux from of apoE in the cholesterol efflux of plasma through the of HDL particles, cellular cholesterol efflux Y. Bellosta S. Pitas R.E. Mahley R.W. Assmann G. von Eckardstein A. of a human apolipoprotein E in cholesterol efflux of apolipoprotein Natl. Acad. Sci. USA. 1998; Scholar). It is that several effects of apoE have been to its to through cell heparan sulfate (7Ishigami M. Swertfeger D.K. Granholm N.A. Hui D.Y. Apolipoprotein E inhibits platelet-derived growth factor-induced vascular smooth muscle cell migration and proliferation by suppressing signal transduction and preventing cell entry to G1 phase.J. Biol. Chem. 1998; 273: 20156-20161Google Scholar, M. Swertfeger D.K. Hui M.S. Granholm N.A. Hui D.Y. Apolipoprotein E inhibition of vascular smooth muscle cell proliferation the inhibition of migration is through activation of oxide Biol. Scholar, M. Swertfeger D.K. Hui M.S. Granholm N.A. Hui D.Y. Apolipoprotein E inhibition of vascular smooth muscle cell proliferation the inhibition of migration is through activation of oxide Biol. Scholar). the of G. Y. A. Apolipoprotein E-containing high density lipoprotein neurite outgrowth and is a for the density lipoprotein Biol. Chem. Scholar) that HDL is a for the cholesterol esterification by was that efflux of both cholesterol and by apoE from and was with or the of apoE heparan sulfate or M. Apolipoprotein E exhibits isoform-specific of lipid efflux from and in Scholar). the a study by S. M. discoidal particles are for the The of ApoE for Biol. Chem. Scholar) had that reconstituted discoidal particles are for the both selective uptake from the lipoprotein to and cellular cholesterol efflux M. efflux to high and density lipoproteins is on lipoprotein to the Biol. Chem. Scholar). Our demonstrate that HDL-LpE particles were present in plasma of normolipidemic and hypoalphalipoproteinemic In HDL-LpE in plasma transfer of apoE the and is efficient of cell-derived cholesterol. study of HDL-LpE with and may provide the mechanism of cholesterol transport in the and in and the effects of apoE in preventing or vascular The to their to and Tremblay for their for were by to from the for and apoE was a from H. of Plasma from the was a from was by from the of and from the with by as of the is the of the in at cholesteryl ester cholesteryl ester transfer protein lipoprotein containing only apoE reverse cholesterol transport disease triglyceride-rich lipoprotein two-dimensional nondenaturing gradient gel electrophoresis

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