Differential effects of HDL subpopulations on cellular ABCA1- and SR-BI-mediated cholesterol efflux

Our objective was to evaluate the associations of individual apolipoprotein A-I (apoA-I)-containing HDL subpopulation levels with ABCA1- and scavenger receptor class B type I (SR-BI)-mediated cellular cholesterol efflux. HDL subpopulations were measured by nondenaturing two-dimensional gel electrophoresis from 105 male subjects selected with various levels of apoA-I in preβ-1, α-1, and α-3 HDL particles. ApoB-containing lipoprotein-depleted serum was incubated with 3Hcholesterol-labeled cells to measure efflux. The difference in efflux between control and ABCA1-upregulated J774 macrophages was taken as a measure of ABCA1-mediated efflux. SR-BI-mediated efflux was determined using cholesterol-labeled Fu5AH hepatoma cells. Fractional efflux values obtained from these two cell systems were correlated with the levels of individual HDL subpopulations. A multivariate analysis showed that two HDL subspecies correlated significantly with ABCA1-mediated efflux: small, lipid-poor preβ-1 particles (P = 0.0022) and intermediate-sized α-2 particles (P = 0.0477). With regard to SR-BI-mediated efflux, multivariate analysis revealed significant correlations with α-2 (P = 0.0004), α-1 (P = 0.0030), preβ-1 (P = 0.0056), and α-3 (P = 0.0127) HDL particles.These data demonstrate that the small, lipid-poor preβ-1 HDL has the strongest association with ABCA1-mediated cholesterol even in the presence of all other HDL subpopulations. Cholesterol efflux via the SR-BI pathway is associated with several HDL subpopulations with different apolipoprotein composition, lipid content, and size. Our objective was to evaluate the associations of individual apolipoprotein A-I (apoA-I)-containing HDL subpopulation levels with ABCA1- and scavenger receptor class B type I (SR-BI)-mediated cellular cholesterol efflux. HDL subpopulations were measured by nondenaturing two-dimensional gel electrophoresis from 105 male subjects selected with various levels of apoA-I in preβ-1, α-1, and α-3 HDL particles. ApoB-containing lipoprotein-depleted serum was incubated with 3Hcholesterol-labeled cells to measure efflux. The difference in efflux between control and ABCA1-upregulated J774 macrophages was taken as a measure of ABCA1-mediated efflux. SR-BI-mediated efflux was determined using cholesterol-labeled Fu5AH hepatoma cells. Fractional efflux values obtained from these two cell systems were correlated with the levels of individual HDL subpopulations. A multivariate analysis showed that two HDL subspecies correlated significantly with ABCA1-mediated efflux: small, lipid-poor preβ-1 particles (P = 0.0022) and intermediate-sized α-2 particles (P = 0.0477). With regard to SR-BI-mediated efflux, multivariate analysis revealed significant correlations with α-2 (P = 0.0004), α-1 (P = 0.0030), preβ-1 (P = 0.0056), and α-3 (P = 0.0127) HDL particles. These data demonstrate that the small, lipid-poor preβ-1 HDL has the strongest association with ABCA1-mediated cholesterol even in the presence of all other HDL subpopulations. Cholesterol efflux via the SR-BI pathway is associated with several HDL subpopulations with different apolipoprotein composition, lipid content, and size. The inverse relationship between plasma levels of HDL, either cholesterol or apolipoprotein A-I (apoA-I) content, and coronary heart disease (CHD) has been demonstrated in many epidemiological, prospective, and intervention studies (1Miller N.E. Thelle D.S. Forde O.H. Mjos O.D. The Tromso Heart Study. High-density lipoprotein and coronary heart disease: a prospective case-control study.Lancet. 1977; 1: 965-968Google Scholar, 2Gordon D.J. Probsfield J.L. Garrison R.J. Neation J.D. Castelly W.P. Knoke J.D. Jacobs D.R. Bangdiwala S. Tyroler H.A. High-density lipoprotein cholesterol and cardiovascular disease: four prospective American studies.Circulation. 1989; 79: 8-15Google Scholar, 3Assmann G. Shulte H. Relation of high-density lipoprotein cholesterol and triglycerides to incidence of atherosclerotic coronary artery disease (the PROCAM experience).Am. J. Cardiol. 1992; 70: 733-737Google Scholar, 4Barter P. Rye K. High density lipoprotein and coronary heart disease.Atherosclerosis. 1996; 121: 1-12Google Scholar, 5Montali A. Vega G.L. Grundy S.M. Concentrations of apolipoprotein A-I-containing particles in patients with hypoalphalipoproteinemia.Arterioscler. Thromb. Vasc. Biol. 1994; 14: 511-517Google Scholar, 6Robins S.J. Collins D. Wittes J.T. Papademetriou V. Deedwania P.C. Schaefer E.J. McNamara J.R. Kashyap M.L. Hershman J.M. Wexler L.F. et al.Veterans Affairs High-Density Lipoprotein Intervention Trial. Relation of gemfibrozil treatment and lipid levels with major coronary events. VA-HIT: a randomized controlled trial.J. Am. Med. Assoc. 2001; 285: 1585-1591Google Scholar). The cardioprotective effect of HDL has been largely attributed to its role in reverse cholesterol transport (RCT), in which cholesterol that has been synthesized or deposited in peripheral tissues is returned to the liver for either recycling or excretion in the bile. This pathway involves several identifiable steps: 1) ApoA-I is synthesized in the liver or small intestine. 2) Phospholipids and cholesterol from cell membranes are transferred to apoA-I in the extracellular space in an ABCA1-dependent process that results in the formation of discoidal HDL (7Fielding C.J. Fielding P.E. Molecular physiology of reverse cholesterol transport.J. Lipid Res. 1995; 36: 211-228Google Scholar, 8von Eckardstein A. Huang Y. Assmann G. Physiological role and clinical relevance of high-density lipoprotein subclasses.Curr. Opin. Lipidol. 1994; 5: 404-416Google Scholar, 9Young S.G. Fielding C.J. The ABCs of cholesterol efflux.Nat. Genet. 1999; 22: 316-318Google Scholar). 3) Free cholesterol (FC) is esterified by the action of LCAT, and the small, discoidal particles are converted to larger, spherical HDL (10Francone O.L. Gurakar A. Fielding C. Distribution and functions of lecithin:cholesterol acyltransferase and cholesteryl ester transfer protein in plasma lipoproteins. Evidence for a functional unit containing these activities together with apolipoproteins A-I and D that catalyzes the esterification and transfer of cell-derived cholesterol.J. Biol. Chem. 1989; 264: 7066-7072Google Scholar). 4) The interaction of spherical HDL with cholesteryl ester transfer protein transfers HDL cholesteryl esters (CEs) to apoB-containing lipoproteins (11Barter P.J. Hugh Sinclair Lecture. The regulation and remodelling of HDL by plasma factors.Atheroscler. Suppl. 2002; 3: 39-47Google Scholar). 5) Cholesterol is transported to the liver, either via the selective uptake of HDL CEs by scavenger receptor class B type I (SR-BI) (direct RCT) or via the uptake of whole LDL by the LDL receptor in the liver (indirect RCT) (12Quintao E.C.R. Is reverse cholesterol transport a misnomer for suggesting its role in the prevention of atherome formation?.Atherosclerosis. 1995; 116: 1-14Google Scholar). Experiments with transgenic animals suggest that disturbances in one or more steps in RCT result in accelerated atherosclerosis, whereas the overexpression of key factors involved in RCT is atheroprotective (13von Eckardstein A. Nofer J.R. Assman G. Acceleration of reverse cholesterol transport.Curr. Opin. Cardiol. 2000; 15: 348-354Google Scholar). Moreover, humans who do secrete apoA-I and have defective ABCA1 have premature CHD (14Ordovas J.M. Cassidy D.K. Civeira F. Bisgaier C.L. Schaefer E.J. Familial apolipoprotein A-I, C-III, and A-IV deficiency and premature atherosclerosis due to deletion of a gene complex on chromosome 11.J. Biol. Chem. 1989; 264: 16339-16342Google Scholar, 15Asztalos B.F. Brousseau M.E. McNamara J.R. Horvath K.V. Roheim P.S. Schaefer E.J. Subpopulations of high density lipoproteins in homozygous and heterozygous Tangier disease.Atherosclerosis. 2001; 156: 217-225Google Scholar). Some investigators believe that HDL has no significant role in RCT, because the amount of cholesterol that HDL carries back to the liver is insignificant compared with the amount carried by apoB-containing lipoproteins (16Osono Y. Woollett L.A. Marotti K.R. Melchior G.W. Dietschy J.M. Centripetal cholesterol flux from extrahepatic organs to the liver is independent of the concentration of high density lipoprotein-cholesterol in plasma.Proc. Natl. Acad. Sci. USA. 1996; 93: 4114-4119Google Scholar, 17Jolley C.D. Woollett L.A. Turley S.D. Dietschy J.M. Centripetal cholesterol flux to the liver is dictated by events in the peripheral organs and not by the plasma high density lipoprotein or apolipoprotein A-I concentration.J. Lipid Res. 1998; 39: 2143-2149Google Scholar). Concentrations of HDL even in the peripheral lymph are far higher than required for any step in RCT (18Reichl D. Lipoproteins of human peripheral lymph.Eur. Heart J. 1990; 11: 230-236Google Scholar, 19Hara H. Yokoyama S. Interaction of free apolipoproteins with macrophages. Formation of high density lipoprotein-like lipoproteins and reduction of cellular cholesterol.J. Biol. Chem. 1991; 266: 3080-3086Google Scholar, 20Sviridov D. Hoang A. Sawyer W.H. Fidge N.H. Identification of a sequence of apolipoprotein A-I associated with the activation of lecithin:cholesterol acyltransferase.J. Biol. Chem. 2000; 275: 19707-19712Google Scholar, 21Wong L. Sivok B. Kurucz E. Sloop C.H. Roheim P.S. Asztalos B. Lipid composition of HDL subfractions in dog plasma and lymph.Arterioscler. Thromb. Vasc. Biol. 1995; 15: 1875-1881Google Scholar). Several investigators have suggested that HDL protects against atherosclerosis as a result of its anti-inflammatory and antioxidant functions as well as its actions in downregulating adhesive molecules on the surface of vascular endothelium and inhibiting platelet aggregation (22Cockerill G.W. Rye K.A. Gamble J.R. Vadas M.A. Barter P.J. High-density lipoproteins inhibit cytokine-induced expression of endothelial cell adhesion molecules.Arterioscler. Thromb. Vasc. Biol. 1995; 15: 1987-1994Google Scholar, 23Watson A.D. Berliner J.A. Hama S.Y. La Du B.N. Faull K.F. Fogelman A.M. Navab M. Protective effect of high density lipoprotein associated paraoxonase. Inhibition of the biological activity of minimally oxidized low density lipoprotein.J. Clin. Invest. 1995; 96: 2882-2891Google Scholar). Although these properties are well documented in vitro, these HDL functions have not yet been unequivocally established in vivo. HDL is a heterogeneous lipoprotein class with different subspecies that vary in apolipoprotein and lipid composition, in size and charge, and in physiological functions (8von Eckardstein A. Huang Y. Assmann G. Physiological role and clinical relevance of high-density lipoprotein subclasses.Curr. Opin. Lipidol. 1994; 5: 404-416Google Scholar, 24Mowri H.O. Patsch W. Smith L.C. Gotto A.M. Patsch J.R. Different reactivities of high-density lipoprotein2 subfractions with hepatic lipase.J. Lipid Res. 1992; 33: 1269-1279Google Scholar, 25Castro G.R. Fielding C.J. Early incorporation of cell-derived cholesterol into pre-β-migrating high-density lipoprotein.Biochemistry. 1988; 27: 25-29Google Scholar, 26Miida T. Kawano M. Fielding C.J. Fielding P.E. Regulation of the concentration of preβ high-density lipoprotein in normal plasma by cell membranes and lecithin-cholesterol acyltransferase activity.Biochemistry. 1992; 31: 11112-11117Google Scholar). We hypothesize that the diverse HDL subpopulations have different roles in RCT. Understanding the role of HDL in RCT is important, especially in light of epidemiological studies demonstrating significant correlations between specific HDL subspecies and the incidence of CHD (27Asztalos B.F. Roheim P.S. Milani R.L. Lefevre M. McNamara J.R. Horvath K.V. Schaefer E.J. Distribution of HDL subpopulations in patients with coronary heart Thromb. Vasc. Biol. 2000; Scholar, B.F. M. Horvath K.V. Schaefer E.J. in HDL concentration in coronary artery Thromb. Vasc. Biol. Scholar, B.F. L.A. S. Horvath K.V. Schaefer E.J. High-density lipoprotein subpopulation and coronary heart disease in male of the Thromb. Vasc. Biol. Scholar). by the α-1 HDL whereas all of the other HDL subpopulations (27Asztalos B.F. Roheim P.S. Milani R.L. Lefevre M. McNamara J.R. Horvath K.V. Schaefer E.J. Distribution of HDL subpopulations in patients with coronary heart Thromb. Vasc. Biol. 2000; Scholar). in have cell surface ABCA1 and as significant factors in HDL A. M. The role of the high-density lipoprotein receptor SR-BI in the lipid of and other Scholar, M.A. S. M. receptor and cholesterol Opin. Lipidol. 1999; Scholar, S. A. S. M. Identification of scavenger receptor SR-BI as a high density lipoprotein 1996; Scholar). the interaction between HDL and these cell surface is Early studies demonstrated that SR-BI the selective transfer of from HDL into cells and the flux of between HDL and the plasma Y. B. Y. M.L. receptor high density cellular cholesterol Biol. Chem. Scholar, S. of scavenger receptor class B type selective uptake of cholesteryl esters from high density lipoprotein to Biol. Chem. 1999; Scholar). many of the of SR-BI-mediated lipid flux efflux and between HDL and the plasma With to the selective uptake of has been that SR-BI functions in a process in which the of HDL to the receptor is to the flux of S. A analysis of apolipoprotein to for and Lipid Res. Scholar, M. of the high density lipoprotein and low density lipoprotein activities of scavenger receptor class B type I using activity Biol. Chem. 2000; 275: Scholar, T. M. The of in and of ApoA-I on scavenger receptor class B type I (SR-BI)-mediated cholesterol efflux suggest that formation of a complex between high density lipoprotein and SR-BI is required for lipid transport.J. Biol. Chem. 2002; Scholar). using HDL and HDL showed that more selective whereas other studies that are to more compared with D. high density lipoprotein particles. to studies of the for selective uptake of cholesterol Biol. Chem. Scholar, S. P. M. M.A. receptor class B type cholesteryl uptake and efflux of of high density lipoprotein size and Biol. Chem. Scholar). HDL size SR-BI-mediated selective the is to selective SR-BI-mediated efflux is particles more cell cholesterol efflux than small particles the concentration S. P. M. M.A. receptor class B type cholesteryl uptake and efflux of of high density lipoprotein size and Biol. Chem. Scholar). has been that in apoA-I in different particles to SR-BI S. P. M. M.A. receptor class B type cholesteryl uptake and efflux of of high density lipoprotein size and Biol. Chem. Scholar). all studies of cell cholesterol efflux as by SR-BI or ABCA1 have of lipoproteins or in cells are to a of HDL particles. We cells to the HDL from individual serum These were by the of apoB-containing lipoproteins using a which not apolipoproteins from HDL particles. the efflux of type of HDL by the correlations between these subpopulations and ABCA1- and SR-BI-mediated cholesterol efflux. Our was that different HDL subpopulations vary significantly in to cellular cholesterol efflux. of 105 male were selected from a of on specific HDL subpopulation levels and 1) low preβ-1 and low α-1 2) low preβ-1 and high α-1 3) low preβ-1 4) high preβ-1 and low α-1 5) high preβ-1 and high α-1 low α-3 and high α-3 of all subjects = and of subjects = selected with various preβ-1, α-1, and α-3 High High lipid and apoA-I levels levels in HDL subpopulations efflux by apolipoprotein scavenger receptor class B type in a apolipoprotein scavenger receptor class B type plasma was from all an was and were measured using was using the ApoA-I were measured with a from HDL subpopulations were determined by nondenaturing two-dimensional gel and as B.F. Lefevre M. M. L. Roheim P.S. subjects with low HDL cholesterol levels have HDL Thromb. Vasc. Biol. Scholar). of plasma was and on a gel in the the from the The gel was and the were nondenaturing the were to for by to membranes for ApoA-I was on the with and against The was in a particles not with any other HDL were of the HDL subpopulations was on the of with than in the size were as particles. HDL subpopulations were and and were measured in and to the of HDL subpopulations. were determined from the high on the gel were as of two ApoA-I of the subpopulations were by by plasma apoA-I subjects were selected on the of preβ-1 in the with HDL subpopulations. in with and and all and were obtained from or as in the and were from and for cell were obtained from was a from were obtained from were obtained from and were obtained as Fu5AH cells were in with serum and J774 macrophages were in with and efflux cells well were on using of the the was with of containing and of the and the cells were incubated in for Fu5AH cells were with cholesterol in containing J774 cells were using containing was by from human serum obtained from human serum were from ApoA-I was obtained from human The was by using a from and P. C. M. and of apolipoproteins A-I and from human high density lipoproteins by Scholar). was from the of the efflux the plasma was and serum was from the as a was to a concentration of in the plasma to the was incubated for and the plasma was by to the serum from these serum were with to apoB-containing lipoproteins by in to a the was by to the containing the HDL lipoprotein SR-BI-mediated cell cholesterol efflux was measured as the of cholesterol from Fu5AH cells to of containing either the serum to or the serum to of apoB-containing lipoproteins as ABCA1-mediated efflux was measured as the difference in of cellular cholesterol to these from J774 control macrophages and J774 macrophages ABCA1 efflux = efflux from cells efflux from control ABCA1 in J774 of the with J774 were incubated for with containing and control J774 cells were incubated for with the the of efflux containing the to all cell were with with and with efflux were in The of the into cell with the was measured as cholesterol into cell was by a of of control and J774 cells not to the serum with cellular cholesterol was measured by in of the and in cholesterol to with Fu5AH cells for or with control and J774 cells for was measured by of of efflux that been efflux values were by the small amount of cholesterol from of and J774 cells incubated with for control human apoA-I and a of human serum were in with the in These were to the efflux values to control for the from Fu5AH cells (SR-BI) was on the of the efflux obtained with the human serum was as a control for SR-BI-mediated efflux. ABCA1-mediated efflux from the J774 cells the efflux obtained with apoA-I for The data were and to were and were to to efflux. all by all of the were and and C.L. Some on 15: were were using the for and evaluate the association of different HDL subpopulations with cellular cholesterol efflux, serum was with to the in to the apoB-containing lipoproteins that to efflux to studies using a of demonstrated that of the apoB-containing lipoproteins of and HDL particles H. of all subjects = and of subjects = selected with various preβ-1, α-1, and α-3 levels are in The apoA-I and levels were in the with high preβ-1 and high α-1 The and levels were in the high α-1 HDL from subjects in the with high preβ-1 and high α-1 the of ABCA1-mediated cholesterol efflux. HDL from subjects in the with low preβ-1 α-1, low α-1, and low the levels of cholesterol efflux via the ABCA1 HDL from subjects selected with high α-1 preβ-1, high the levels of cholesterol efflux via the SR-BI a preβ-1 (P = and α-2 (P = were significantly to ABCA1-mediated cholesterol efflux multivariate the between ABCA1-mediated efflux and preβ-1 (P = 0.0022) and α-2 (P = were We with all of HDL particles. of the suggested a role for preβ-1 and α-2 in ABCA1-mediated cholesterol efflux. The that all HDL particles as of ABCA1-mediated efflux an of (P = The containing preβ-1 an of Moreover, that preβ-1 an of or whereas that preβ-1 an The containing preβ-1 and α-2 an of and were the correlated significantly with the cholesterol efflux via the ABCA1 pathway not and multivariate of ABCA1-mediated cholesterol efflux from J774 macrophages on HDL in a SR-BI-mediated cholesterol efflux was in a significant associations between efflux levels and preβ-1, α-1, and multivariate the associations between SR-BI-mediated cholesterol efflux and preβ-1, α-1, and α-3 levels were many that were in of the not values all of preβ-1, α-1, and α-3 were in the and were that the correlated significantly with the cholesterol efflux via the SR-BI pathway not and multivariate of SR-BI-mediated cholesterol efflux from Fu5AH cells on HDL in a a the levels of HDL were against ABCA1- and SR-BI-mediated cholesterol efflux and the of the was ABCA1-mediated cholesterol efflux showed a significant relationship with the preβ-1 SR-BI-mediated cholesterol efflux values showed significant associations with four HDL preβ-1, α-1, and α-2 is that even α-3 not have significant on its significantly the association between α-1 levels and SR-BI-mediated cholesterol efflux. α-1 and α-3 values of and were in a for these two HDL particles the higher than that for α-2 which the α-1 and α-3 together SR-BI-mediated efflux than suggested by individual the of α-1, and SR-BI-mediated efflux We the to the surface of from different of the This analysis that α-3 into the α-1 the analysis of scavenger receptor class B type I (SR-BI)-mediated cholesterol efflux from Fu5AH hepatoma cells and levels of various HDL between SR-BI-mediated from Fu5AH hepatoma cells and levels of HDL particles α-1, and from the of all efflux, α-1 and α-3 from the of SR-BI-mediated efflux and α-1 from the of SR-BI-mediated efflux and α-3 from the of SR-BI-mediated efflux and α-1 levels the α-3 surface is to The between B and D that α-3 levels the between α-1 and SR-BI-mediated The role of HDL in RCT has been is not RCT involves all HDL factors cholesteryl ester transfer transfer and two cell surface which the flux of cholesterol of and which the flux of and the of are whole whole HDL or specific HDL preβ-1, and HDL particles with a of cholesterol efflux from cells. is no on correlations of individual HDL particles and cholesterol efflux are as a as in the HDL cholesterol efflux via the ABCA1 and SR-BI and these efflux data to the concentration of individual HDL determined by two-dimensional nondenaturing gel and Our objective was to evaluate the associations between levels of individual HDL subpopulations and ABCA1- and SR-BI-mediated cholesterol efflux. HDL obtained from subjects with high preβ-1 and high α-1 levels the ABCA1-mediated cholesterol efflux. the HDL of subjects with low preβ-1 and high α-1 levels not cholesterol efflux via the ABCA1 We hypothesize that factors other than HDL levels ABCA1-mediated cholesterol efflux as These factors the lipid apolipoprotein composition of HDL which the of preβ-1 to larger, more particles. data that lipoproteins inhibit ABCA1-mediated cholesterol efflux from macrophages A.M. A. lipoproteins inhibit cholesterol efflux to apolipoprotein from human Scholar). with high preβ-1 and high α-1 levels have than have than lipoprotein and on ABCA1-mediated cholesterol efflux to whole serum showed the plasma with high preβ-1 and high α-1 levels more cholesterol efflux than other via the ABCA1 pathway not to ABCA1-mediated cholesterol efflux, several individual HDL subpopulations α-1, and were significantly associated with cholesterol efflux via the SR-BI The of SR-BI-mediated cholesterol efflux was in subjects with high preβ-1 and high α-1 to a high α-1 the of α-2 more than the of all α-1 and α-2 levels were correlated with SR-BI-mediated cholesterol the levels of α-1 and α-2 the for the efflux SR-BI has a by selective cholesterol uptake from HDL and cholesterol efflux to the to cholesterol efflux to HDL via the SR-BI We do not these data are to selective cholesterol uptake from The two small, lipid-poor HDL particles and do not significant of cholesterol to cells via We hypothesize that the two HDL subpopulations α-1 and containing the of HDL are more than for SR-BI-mediated selective cholesterol to α-1, α-2 is an and was to the and selective lipid uptake from by SR-BI M. L. W. L. A. J. D.R. SR-BI and the association of HDL with class B scavenger SR-BI and Lipid Res. Scholar). This that selective uptake compared with these particles do not the lipid and apolipoprotein composition of α-1 and α-2 particles. We believe that α-2 is a in RCT because α-2 levels are two to higher than α-1 levels in normal human plasma and even higher in in which α-1 levels are α-2 levels are to normal (27Asztalos B.F. Roheim P.S. Milani R.L. Lefevre M. McNamara J.R. Horvath K.V. Schaefer E.J. Distribution of HDL subpopulations in patients with coronary heart Thromb. Vasc. Biol. 2000; Scholar, B.F. M. Horvath K.V. Schaefer E.J. in HDL concentration in coronary artery Thromb. Vasc. Biol. Scholar, B.F. L.A. S. Horvath K.V. Schaefer E.J. High-density lipoprotein subpopulation and coronary heart disease in male of the Thromb. Vasc. Biol. Scholar). the for HDL subpopulations with different is is an for the role of these HDL subpopulations in CHD and α-1 levels B.F. M. Horvath K.V. Schaefer E.J. in HDL concentration in coronary artery Thromb. Vasc. Biol. Scholar, B.F. Horvath K.V. McNamara J.R. Roheim P.S. Schaefer E.J. of on the HDL subpopulation of coronary heart disease Lipid Res. 2002; Scholar). data on apoA-I and HDL that these preβ-1 Our data that in the Affairs HDL Intervention gemfibrozil α-2 levels We that SR-BI-mediated cholesterol efflux from hepatoma cells is significantly associated with the α-1 and α-2 HDL whereas the ABCA1-mediated efflux from macrophages is significantly associated with the lipid-poor preβ-1 measured associations between HDL levels and cholesterol efflux. The relationship and the have to by HDL subpopulations with the cells. This was by from the of and to and and and