Age-related impairment of HDL-mediated cholesterol efflux

Our aim in this study was to investigate the effect of aging on the capacity of HDLs to promote reverse cholesterol transport. HDLs were isolated from plasma of young (Y-HDL) and elderly (E-HDL) subjects. HDL-mediated cholesterol efflux was studied using THP-1 and J774 macrophages. Our results show that E-HDLs present a lower capacity to promote cholesterol efflux than Y-HDLs (41.7 ± 1.4% vs. 49.0 ± 2.2%, respectively; P = 0.013). Reduction in the HDL-mediated cholesterol efflux capacity with aging was more significant with HDL3 than HDL2 (Y-HDL3, 57.3 ± 1% vs. E-HDL3, 50.9 ± 2%; P = 0.012). Moreover, our results show that ABCA1-mediated cholesterol efflux is the more affected pathway in terms of cholesterol-removing capacity. Interestingly, the composition and structure of HDL revealed a reduction in the phosphatidylcholine-sphingomyelin ratio (E-HDL, 32.7 ± 2.7 vs. Y-HDL, 40.0 ± 1.9; P = 0.029) and in the phospholipidic layer membrane fluidity in E-HDL compared with Y-HDL as well as an alteration in the apolipoprotein A-I structure and charge. In conclusion, our results shown that E-HDLs present a reduced capacity to promote cholesterol efflux, principally through the ABCA1 pathway, and this may explain the increase of the incidence of cardiovascular diseases observed during aging. Our aim in this study was to investigate the effect of aging on the capacity of HDLs to promote reverse cholesterol transport. HDLs were isolated from plasma of young (Y-HDL) and elderly (E-HDL) subjects. HDL-mediated cholesterol efflux was studied using THP-1 and J774 macrophages. Our results show that E-HDLs present a lower capacity to promote cholesterol efflux than Y-HDLs (41.7 ± 1.4% vs. 49.0 ± 2.2%, respectively; P = 0.013). Reduction in the HDL-mediated cholesterol efflux capacity with aging was more significant with HDL3 than HDL2 (Y-HDL3, 57.3 ± 1% vs. E-HDL3, 50.9 ± 2%; P = 0.012). Moreover, our results show that ABCA1-mediated cholesterol efflux is the more affected pathway in terms of cholesterol-removing capacity. Interestingly, the composition and structure of HDL revealed a reduction in the phosphatidylcholine-sphingomyelin ratio (E-HDL, 32.7 ± 2.7 vs. Y-HDL, 40.0 ± 1.9; P = 0.029) and in the phospholipidic layer membrane fluidity in E-HDL compared with Y-HDL as well as an alteration in the apolipoprotein A-I structure and charge. In conclusion, our results shown that E-HDLs present a reduced capacity to promote cholesterol efflux, principally through the ABCA1 pathway, and this may explain the increase of the incidence of cardiovascular diseases observed during aging. The inverse relationship between plasma levels of HDLs and cardiovascular disease has been demonstrated in several epidemiological and interventional studies (1Wilson P.W. Abbott R.D. Castelli W.P. High density lipoprotein cholesterol and mortality. The Framingham Heart Study. Arteriosclerosis. 1988; 8: 737-741Google Scholar, 2Thom T. Haase N. Rosamond W. Howard V.J. Heart disease and stroke statistics—2006 update. A report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation. and the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. 2006; 113: 85-151Google Scholar). The antiatherogenic properties of HDL have been ascribed to their abilities to inhibit LDL oxidation (3Parthasarathy 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) and to prevent oxidized LDL-induced cytotoxicity and monocyte transmigration (4Suc I. Escargueil-Blanc I. Troly M. Salvayre R. Nègre-Salvayre A. HDL and apoA-I prevent cell death of endothelial cells induced by oxidized LDL. Arterioscler. Thromb. Vasc. Biol. 1997; 17: 2158-2166Google Scholar, 5Wang N. Lan D. Chen W. Mastuura F. Tall A.R. ATP-binding cassette transporters G1 and G4 mediate cellular cholesterol efflux to high-density lipoproteins. Proc. Natl. Acad. Sci. USA. 2004; 101: 9774-9779Google Scholar). One of the long-standing mechanisms to explain the protective effect of HDLs against cardiovascular disease is their capacity to promote reverse cholesterol transport (RCT) (6Kennedy M.A. Barrera G.C. Nakamura K. Baldan A. Tarr P. Fishbein M.C. Frank J. Francone O.L. Edwards P.A. ABCG1 has a critical role in mediating cholesterol efflux to HDL and preventing cellular lipid accumulation. Cell Metab. 2005; 2: 121-131Google Scholar). The concept of RCT, as suggested by Glomset (7Glomset J.A. The plasma lecithins cholesterol acyltransferase reaction. J. Lipid Res. 1968; 9: 155-167Google Scholar), consists of the movement of cholesterol from the peripheral tissues to the liver, which starts by the efflux of free cholesterol (FC) and phospholipids from cells of peripheral tissues to preβ-migrating lipid-poor or lipid-free apolipoprotein A-I (apoA-I) and to HDL3 (7Glomset J.A. The plasma lecithins cholesterol acyltransferase reaction. J. Lipid Res. 1968; 9: 155-167Google Scholar, 8Castro G.R. Fielding C.J. Early incorporation of cell-derived cholesterol into pre-beta-migrating high-density lipoprotein. Biochemistry. 1988; 27: 25-29Google Scholar, 9Bortnick A.E. Rothblat G.H. Stoudt G. Hoppe K.L. Royer L.J. McNeish J. Francone O.L. The correlation of ATP-binding cassette 1 mRNA levels with cholesterol efflux from various cell lines. J. Biol. Chem. 2000; 275: 28634-28640Google Scholar). The process of FC efflux occurs by three known pathways. 1) Aqueous diffusion. This process involves the desorption of FC molecules from the donor lipid-water interface and diffusion of these molecules through the intervening aqueous phase until they collide with and are absorbed by an acceptor. 2) Scavenger receptor class B type I (SR-BI)-mediated FC flux. The movement of FC via SR-BI is bidirectional, and like the aqueous diffusion mechanism, the net movement of FC via SR-BI depends on the direction of the cholesterol gradient (10de la Llera-Moya M. Connelly M.A. Drazul D. Klein S.M. Favari E. Yancey P.G. Williams D.L. Rothblat G.H. Scavenger receptor class B type I affects cholesterol homeostasis by magnifying cholesterol flux between cells and HDL. J. Lipid Res. 2001; 42: 1969-1978Google Scholar). 3) ATP binding cassette-mediated cholesterol efflux. ABCA1 and ABCG1/4 are members of a large family of ATP-dependent transporters that share common structural motifs for the active transport of a variety of substrates (11Dean M. Hamon Y. Chimini G. The human ATP-binding cassette (ABC) transporter superfamily. J. Lipid Res. 2001; 42: 1007-1017Google Scholar). In contrast to aqueous diffusion and SR-BI-mediated FC flux, the movement of FC by ABCA1 and ABCG1/4 is unidirectional, and net efflux of cellular FCs would always occur via this mechanism (12Yancey P.G. de la Llera-Moya M. Swarnakar S. Monzo P. Klein M.S. Connelly A. Johnson W.J. Williams D.L. Rothblat G.H. 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: 36596-36604Google Scholar). The preferred cholesterol acceptors for ABCA1 are lipid-poor apolipoproteins and all of the exchangeable apolipoproteins, such as apoA-I, apoA-II, apoA-IV, apoE, and apoC (13Remaley A.T. Stonik J.A. Demosky S.J. Neufeld E.B. Bocharov A.V. Vishnyakova T.G. Eggerman T.L. Patterson A.P. Duverger N.J. Santamarina-Fojo S. Apolipoprotein specificity for lipid efflux by the human ABCAI transporter. Biochem. Biophys. Res. Commun. 2001; 280 (et al.): 818-823Crossref PubMed Scopus (278) Google Scholar). ABCA1 has been shown to bind with apoA-I, indicating a very close association between the two proteins in mediating the cholesterol efflux process (14Oram J.F. Lawn R.M. Garvin M.R. Wade D.P. ABCA1 is the cAMP-inducible apolipoprotein receptor that mediates cholesterol secretion from macrophages. J. Biol. Chem. 2000; 275: 34508-34511Google Scholar). Recently, it was shown that another transporter, ABCG1, promotes mass cholesterol efflux from cells to mature HDL particles (HDL2 and HDL3) but not to lipid-poor apoA-I (5,6). Both ABCA1 and ABCG1 are abundant in macrophages, especially after cholesterol loading, suggesting their importance for the cholesterol efflux process. Cholesterol efflux was also correlated to HDL lipid composition and structure (12Yancey P.G. de la Llera-Moya M. Swarnakar S. Monzo P. Klein M.S. Connelly A. Johnson W.J. Williams D.L. Rothblat G.H. 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: 36596-36604Google Scholar). As an example, phosphatidylcholine (PC)-enriched HDL increases cholesterol efflux, whereas sphingomyelin (SPM)-enriched HDL cholesterol to (12Yancey P.G. de la Llera-Moya M. Swarnakar S. Monzo P. Klein M.S. Connelly A. Johnson W.J. Williams D.L. Rothblat G.H. 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: 36596-36604Google Scholar). Moreover, several that are common of HDL are known to the fluidity of lipid and W.J. Rothblat G.H. M.C. Cholesterol transport between cells and high-density lipoproteins. Biochim. Biophys. Acta. Scholar). the phospholipid composition of is known to have but on the fluidity of the lipoprotein phospholipidic layer W.J. Rothblat G.H. M.C. Cholesterol transport between cells and high-density lipoproteins. Biochim. Biophys. Acta. Scholar, R. M. of on the fluidity of human high-density of the composition and phospholipid Biochim. Biophys. Acta. 1990; Scholar). may the of HDL particles to FC molecules that have from peripheral oxidative of HDL capacity to promote cholesterol efflux D. A. R. J. M. in human density oxidized by Biochim. Biophys. Acta. Scholar). the of lipid is with of the properties of HDL and especially a in the fluidity of the HDL phospholipid layer D. A. R. J. M. in human density oxidized by Biochim. Biophys. Acta. Scholar). In have demonstrated that HDLs from elderly are more to lipid A. T. of high-density to in oxidation induced by of Scholar) and present a significant reduction of their with a in 1 de M. M. T. A. in high-density is to an alteration in the free 2006; Scholar). In this the capacity of HDL to promote cholesterol efflux during aging with the aim of the and that this process. our results to a of the increase in the incidence of cardiovascular and were from and were from THP-1 and J774 cells were from the American was from and are shown in 1 were they were and of or were free of and was were all and of the was for The elderly were and The Committee of the the and all and of the study ± ± mass ± ± ± ± ± ± ± ± ± ± ± ± ± ± are ± in a are ± plasma was in and HDL were to the of and W. D. R. of and of their by Scholar). were in and the were by was from HDLs from young and elderly to the of M. M. J. ABCA1 and promotes cholesterol efflux from J. Lipid Res. Scholar). HDLs were in and the were to using two were and in and in THP-1 and J774 were in and The were with for and of THP-1 into was induced by the cells a density of in the of for THP-1 and J774 were in for cells were and in 1% for of The cells were and to 1) HDL 2) and 3) HDL3 or from young and elderly subjects. In another of J774 were with for The cells were and with in or with for to cells S. M. J. modification of plasma HDL by phospholipids promotes ABCA1-mediated cholesterol J. Lipid Res. 2005; Scholar). the cells were and for in the of HDL and or apoA-I from young and elderly subjects. Cholesterol efflux was by and the of cholesterol cholesterol was as in in the cell cholesterol efflux was also by cell cholesterol mass cellular were from J774 cells with and the phase was cholesterol in cells as well as in were by the of and E. of and cholesterol in Biol. 27: PubMed Scopus Google Scholar). of cell proteins was and by were with against ABCA1 was against the and was using a was from J774 cells using the and reverse using the was for with the ABCA1 and ABCG1 were in was as using as an A. T. of in density and role in the of density to lipid J. Lipid Res. 2000; Scholar). HDL was to the of as D. A. R. J. M. in human density oxidized by Biochim. Biophys. Acta. Scholar). were by to R. of in J. Scholar). was as by of structural proteins during the of the of Scholar) on was with of of or oxidized HDL and were with were also by the HDL and for the of apoA-I modification of HDL (apoA-I) results in an increase in net which using lipoprotein was as the ratio of the of the to that of HDL of young of an increase of the compared with HDL was in on The were with in was as by D. A. I. S. of in 1990; Scholar). apoA-I was from HDL as D. A. I. S. of in 1990; Scholar). The were by were in by = fluidity was by of as R. S. of and membrane fluidity by in and endothelial Res. Scholar). the inverse of and is as was as and are the and and is the were using a of and J. A. for and of from J. Biol. Chem. Scholar). One of lipid was into an to an to the of and J. of phospholipids by with a to for J. High Res. Scholar). were to a gradient are as ± was for was to the association between two and the was to the between two were using The of are in The two significant in their mass or LDL and HDL were in the for young and elderly and the phase was levels for the effect of aging on the antiatherogenic of HDL and their to promote RCT, the capacity of HDL from young (Y-HDL) and elderly (E-HDL) to cholesterol efflux. A on cholesterol efflux revealed between Y-HDL and E-HDL that were with HDL after of 1 In Y-HDL and E-HDL were for with THP-1 with cholesterol efflux by Y-HDL was by than that by The of cholesterol efflux by Y-HDL and E-HDL were on the with and a after of this is in with results by and Y. T. High density lipoprotein effect to efflux of cholesterol from cells after oxidative Proc. Natl. Acad. Sci. USA. Scholar). The of cholesterol mass in the and in cells also demonstrated a significant capacity of Y-HDL to mediate net cholesterol efflux than E-HDL = more into the effect of aging on HDL-mediated cholesterol efflux, the capacity of HDL to promote cholesterol efflux, in HDL2 and our HDL2 and HDL3 were isolated by which the of in our role in the of the capacity between young and elderly M. G. Y. M. K. D. M. The apoA-I of and HDL is by J. Lipid Res. Scholar, D. K. A. I. P. of the role of in cholesterol efflux using isolated HDL. Arterioscler. Thromb. Vasc. Biol. Scholar). to which HDL (HDL2 or HDL3) was more in the HDL-mediated cholesterol efflux from macrophages, and the effect of aging in this process. and HDL3 isolated from young and elderly were for with THP-1 macrophages. induced a efflux P than that induced by whereas were between and as a of a capacity to promote cholesterol efflux than P with observed between and which of the cholesterol efflux was more affected by the mechanism on the ABCA1 using a cell J774 cells ABCA1 compared with THP-1 A.E. Rothblat G.H. Stoudt G. Hoppe K.L. Royer L.J. McNeish J. Francone O.L. The correlation of ATP-binding cassette 1 mRNA levels with cholesterol efflux from various cell lines. J. Biol. Chem. 2000; 275: 28634-28640Google Scholar), as by our results Interestingly, Y-HDL and E-HDL were with J774 cells during was effect of aging on the capacity of HDL to promote cholesterol efflux compared with the THP-1 cells induced of ABCA1 by J774 to the effect of aging on the ABCA1 cholesterol Our results that J774 cells with have a of ABCA1 compared with cells Interestingly, the of of ABCG1 by was The induced of ABCA1 in J774 cells by M. M. J. ABCA1 and promotes cholesterol efflux from J. Lipid Res. Scholar, M. R. M. 1 is a more and of cholesterol efflux, present in HDL than in to 2006; Scholar, P.G. A.E. G. de la Llera-Moya M. M.C. Rothblat G.H. of of cellular cholesterol efflux. Arterioscler. Thromb. Vasc. Biol. PubMed Scopus Google Scholar) and cholesterol efflux in young and elderly whereas were observed in cholesterol efflux as a of aging not Moreover, in J774 Y-HDL cholesterol efflux by compared with whereas cholesterol efflux by compared with from young and elderly was also for capacity to promote cholesterol efflux Our results not shown an effect of aging on the cholesterol efflux from J774 in J774 was mediating cholesterol efflux than = The ABCA1-mediated cholesterol efflux pathway is on the of apoA-I with the ABCA1 alteration or modification of apoA-I the HDL cholesterol efflux capacity. this to the apoA-I modification as a of aging. Interestingly, for the HDL in terms of Y-HDL demonstrated a apoA-I than E-HDL of Y-HDL and E-HDL to oxidative induced by and by the of apoA-I by in a reduction in the apoA-I as shown in oxidative and the apoA-I was reduced as of the oxidative The also demonstrated an alteration of the apoA-I as a of aging and HDL oxidation In our results show that was in than in ± vs. ± P = as a of aging vs. and HDL oxidation and with ± with for 1 ± ± with for ± ± with for ± ± and HDLs isolated from young and elderly are as the of compared with that of the Y-HDL are as for in a Y-HDL and HDLs isolated from young and elderly are as the of compared with that of the Y-HDL are as for modification of Y-HDL and E-HDL a significant reduction of HDL capacity to promote cholesterol efflux is that for the of oxidation of and 1 Y-HDLs show a capacity to promote cholesterol efflux than E-HDLs Interestingly, of HDL oxidation as a of the of an of HDL to lipid with as by the phase for and of aging on the of HDL to lipid phase ± ± phase ± ± were isolated from young and elderly and were oxidized by with phase was as the which or or was was with to young subjects. are as ± of or more in a HDLs were isolated from young and elderly and were oxidized by with phase was as the which or or was was with to young subjects. are as ± of or more investigate the of HDL on cholesterol efflux capacity as a of the HDL phospholipid and as an for HDL phospholipid the phospholipid on the of the HDL This was shown to HDL-mediated cholesterol efflux capacity (12Yancey P.G. de la Llera-Moya M. Swarnakar S. Monzo P. Klein M.S. Connelly A. Johnson W.J. Williams D.L. Rothblat G.H. 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: 36596-36604Google Scholar, The effect of phospholipid on lipoprotein and Scholar) as an a significant in the ratio in HDLs from elderly compared with from young = results were for compared with = Y-HDL was to have and significant phospholipidic layer fluidity than E-HDL The results were for = and = compared with the HDL from elderly The of and the incidence of increase with aging and are for the of cardiovascular and in the High plasma levels of HDLs are with a of an effect to their role in efflux of FC from cell to acceptors is to of the in the process of is by the of several and that HDL structure and A. T. of high-density to in oxidation induced by of Scholar, I. G. E. T. A. of the HDL with aging. 2004; Scholar, A. R. structure and Biochim. Biophys. Acta. PubMed Scopus Google Scholar). studies from our have shown an increase of HDL to lipid and a of HDL with aging A. T. of high-density to in oxidation induced by of Scholar, de M. M. T. A. in high-density is to an alteration in the free 2006; Scholar). the of aging on the process by the antiatherogenic properties of HDL. Our results a significant reduction of the HDL capacity to promote cholesterol efflux from macrophages. which HDL was more HDL2 and HDL3 were isolated and for their capacity to mediate cholesterol efflux. Interestingly, the reduction in the cholesterol efflux with aging was significant for Moreover, in the young a in the capacity of HDL and to promote cholesterol efflux was demonstrated P = significant was observed between and The of HDL3 to increase cellular cholesterol efflux has been to the of J.F. M.C. The of of density lipoprotein on cholesterol efflux from of density lipoprotein receptor J. Biol. Chem. Scholar), phospholipidic ratio in and R. M. cholesterol efflux from human to phospholipid and of Arterioscler. Thromb. Scholar). Moreover, ABCA1 by binding to and with lipid-poor apoA-I, another that explain the between the Y-HDL and E-HDL The of our in more than cell type was to the of the ABCA1 role in the between Y-HDL and and especially between and to promote cholesterol efflux as a of aging. J774 cells were was observed between Y-HDL and E-HDL or between and in which is not the with THP-1 macrophages. This to the in the of ABCA1 between the two cell or to in the of lipid-free apoA-I from the two HDL Moreover, that ABCA1 a with apoA-I by binding the apolipoprotein (14Oram J.F. Lawn R.M. Garvin M.R. Wade D.P. ABCA1 is the cAMP-inducible apolipoprotein receptor that mediates cholesterol secretion from macrophages. J. Biol. Chem. 2000; 275: 34508-34511Google Scholar, N. D.L. Tall A.R. ATP-binding cassette transporter as a cholesterol efflux J. Biol. Chem. 2001; Scholar). of apoA-I that occur with aging may the to the reduction of cholesterol efflux. which affected by a reduction in as well as by a structural may cholesterol efflux capacity. a reduction in the apoA-I in E-HDL compared with Y-HDL, which a reduction in apoA-I in the as was demonstrated I. G. E. T. A. of the HDL with aging. 2004; Scholar). for the Y-HDL as well as E-HDL were the which the reduction in apoA-I to a reduction of significant in apoA-I was between young and elderly Interestingly, HDL with induced a significant reduction of apoA-I and an increase in the apoA-I charge. the apoA-I oxidative with were more for E-HDL than for these results that the alteration of apoA-I as by the and as well as by the increase in of oxidative Moreover, they in the as a of aging in the ABCA1-mediated cholesterol efflux capacity of HDL. our results show that in young and elderly the capacity of HDL to FC from with levels of HDL Interestingly, for the of HDL cholesterol efflux capacity was for Y-HDL than for Moreover, HDL oxidation an apoA-I alteration and HDL phospholipidic layer the levels of cholesterol efflux from is also on the and of HDL to the ABCA1-mediated cholesterol efflux, the ABCG1 and the and the SR-BI all cholesterol to principally HDL2 reverse cholesterol the for phosphatidylcholine 2005; Scholar). that alteration or in the HDL phospholipid composition or structure would reverse cholesterol the for phosphatidylcholine 2005; Scholar, F. A.E. R. HDL from the of membrane fluidity and to a in free cholesterol efflux from human THP-1 macrophages. Biochim. Biophys. Acta. Scholar, I. S. G. E. of density cholesterol efflux from J774 role of scavenger A and J. Cell Sci. Scholar). of the and HDL3 phospholipid composition as a of donor a significant in the ratio in the The increase of was demonstrated to the N. A. P. A. N. of the relationship between and on the efflux capacity of in the 2001; Scholar). by the of reduced HDL in to the oxidative that occur with as shown for HDL-mediated cholesterol efflux capacity has been demonstrated to reduced in R. in high-density lipoprotein and reverse cholesterol transport in and type role of acyltransferase and lipid J. Scholar), in with HDL M. J.F. J. cholesterol transport and efflux in are in with HDL Arterioscler. Thromb. Vasc. Biol. Scholar), and in disease J.F. of cellular cholesterol and phospholipids by apolipoprotein in J. Scholar) and has been with an alteration in HDL or composition and In studies have shown that HDL-mediated cholesterol efflux is by through lipid K. M. Y. M. T. Cholesterol efflux effect of density lipoprotein is by through lipid Biol. Scholar). cholesterol efflux affected by the of 1 and and M. R. M. 1 is a more and of cholesterol efflux, present in HDL than in to 2006; Scholar) demonstrated a of 1 in reverse cholesterol efflux from macrophages. Interestingly, a study from our has shown a significant reduction of 1 in the elderly de M. M. T. A. in high-density is to an alteration in the free 2006; Scholar). Moreover, ABCG1 and cholesterol efflux, especially to HDL2 and HDL3 but not to lipid-poor apoA-I N. Lan D. Chen W. F. Tall A.R. ATP-binding cassette transporters G1 and G4 mediate cellular cholesterol efflux to high-density lipoproteins. Proc. Natl. Acad. Sci. USA. 2004; 101: 9774-9779Google Scholar). In this the HDL that occur during aging may the between HDL and to an of cholesterol efflux. The relationship between ABCG1/4 and cholesterol efflux during aging In to these ATP-dependent Y. N. Y. M.C. Rothblat G.H. Tall A.R. Scavenger receptor promotes density cellular cholesterol efflux. J. Biol. Chem. 1997; Scholar) have that SR-BI promotes a flux between cells and HDL and also net cholesterol efflux to and HDL but not to lipid-poor W. Yancey P.G. Y. S. of scavenger receptor class B type I promotes in apolipoprotein Circulation. Scholar) demonstrated that SR-BI in cholesterol efflux to HDL compared with macrophages, suggesting that SR-BI not have a major role in cholesterol efflux to HDL. In our results have shown an of HDL-mediated capacity with aging that has been to a reduction in the ABCA1 on these that the cholesterol efflux is the more affected pathway with aging and is principally to the oxidative of apoA-I that occur during aging. HDL and are also in the reduction of capacity to mediate cholesterol efflux in the the results not to the of cholesterol efflux that to ABCG1/4 or that HDL structure and composition also these of cholesterol efflux. In conclusion, the reduced capacity of E-HDL to promote cholesterol efflux may explain the increase in the incidence of cardiovascular diseases observed during aging. This was by a from the of is the of a from the in is a of the de The for critical of the with

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