Key points are not available for this paper at this time.
This study tests the hypothesis that autoantibodies to oxidation epitopes on oxidized LDL (OxLDL) promote the clearance of OxLDL from the plasma. Human LDL (hLDL) was injected into immune-competent apolipoprotein E-deficient (apoE−/−) mice and immune-deficient apoE−/−/recombination-activating gene-deficient mice that lack mature T and B cells and thus antibodies. There was a progressive decrease in human apoB-100 in the plasma in all mice, but the rate of clearance was not greater in the immune-competent mice than in the immune-deficient mice. Interestingly, oxidized phospholipid (OxPL) epitopes as detected by the EO6 antibody on the hLDL increased over time, suggesting de novo oxidation of the LDL or transfer of OxPL to the particles. Because the native LDL was not extensively modified, we also examined the clearance of copper OxLDL. Although the extensively OxLDL was cleared faster than the native LDL, there was no difference in the rate of clearance as a function of immune status. There appeared to be some transfer of OxPL to the endogenous murine LDL.Together, these results suggest that oxidation-specific antibodies do not participate to any great extent in the clearance of OxLDL from plasma. However, it is possible that such antibodies may bind to oxidation epitopes and modulate lesion formation within the vessel wall. This study tests the hypothesis that autoantibodies to oxidation epitopes on oxidized LDL (OxLDL) promote the clearance of OxLDL from the plasma. Human LDL (hLDL) was injected into immune-competent apolipoprotein E-deficient (apoE−/−) mice and immune-deficient apoE−/−/recombination-activating gene-deficient mice that lack mature T and B cells and thus antibodies. There was a progressive decrease in human apoB-100 in the plasma in all mice, but the rate of clearance was not greater in the immune-competent mice than in the immune-deficient mice. Interestingly, oxidized phospholipid (OxPL) epitopes as detected by the EO6 antibody on the hLDL increased over time, suggesting de novo oxidation of the LDL or transfer of OxPL to the particles. Because the native LDL was not extensively modified, we also examined the clearance of copper OxLDL. Although the extensively OxLDL was cleared faster than the native LDL, there was no difference in the rate of clearance as a function of immune status. There appeared to be some transfer of OxPL to the endogenous murine LDL. Together, these results suggest that oxidation-specific antibodies do not participate to any great extent in the clearance of OxLDL from plasma. However, it is possible that such antibodies may bind to oxidation epitopes and modulate lesion formation within the vessel wall. It is now established that 65–75% of the clearance of native LDL in vivo is mediated by the LDL receptor pathway, primarily in the liver (1Pittman R.C. Carew T.E. Attie A.D. Witztum J.L. Watanabe Y. Steinberg D. Receptor-dependent and receptor-independent degradation of low density lipoprotein in normal rabbits and in receptor-deficient mutant rabbits.J. Biol. Chem. 1982; 257: 7994-8000Google Scholar). The fact that macrophage foam cell formation and atherosclerosis are greatly accelerated in animals or human subjects with complete genetic deficiency of the LDL receptor focused attention on alternative pathways and led to the recognition of scavenger receptors that bound modified LDL (2Goldstein J.L. Ho Y.K. Basu S.K. Brown M.S. Binding site on macrophages that mediates uptake and degradation of acetylated low density lipoprotein, producing massive cholesterol deposition.Proc. Natl. Acad. Sci. USA. 1979; 76: 333-337Google Scholar), such as oxidized LDL (OxLDL). Although the enhanced uptake of OxLDL by macrophages originally attracted attention to the oxidation of LDL as a major atherogenic factor, it is now appreciated that OxLDL and its many oxidized lipid moieties contribute to atherosclerosis by numerous proinflammatory mechanisms, such as the induction of chemotaxis of monocytes and T cells, and by the induction of proinflammatory and proatherogenic genes in vascular wall cells (3Glass C.K. Witztum J.L. Atherosclerosis: the road ahead.Cell. 2001; 104: 503-516Google Scholar, 4Lusis A.J. Atherosclerosis.Nature. 2000; 407: 233-241Google Scholar, 5VanderLaan P.A. Reardon C.A. Getz G.S. Site specificity of atherosclerosis. Site-selective responses to atherosclerotic modulators.Arterioscler. Thromb. Vasc. Biol. 2004; 24: 12-22Google Scholar). OxLDL is taken up by macrophages by a variety of scavenger receptors (6Steinberg D. Oxidative modification of LDL and atherogenesis.Circulation. 1997; 95: 1062-1071Google Scholar). Although these pathways represent a mechanism by which the formation of foam cells occurs, they also represent pathways mediating the clearance of OxLDL from the circulation. Oxidation of LDL results in the formation of a variety of oxidation-specific neoepitopes that lead to immune responses. In addition, atherogenesis in both experimental animals and humans is associated with increased concentrations of autoantibodies to epitopes of OxLDL (7Salonen J.T. Yla-Herttuala D. Yamamoto R. Butler S. Korpela H. Salonen R. Nyyssonen K. Palinski W. Witztum J.L. Autoantibody against oxidised LDL and progression of carotid atherosclerosis.Lancet. 1992; 339: 883-887Google Scholar, 8Virella G. Virella I. Leman R.B. Pryor M.B. Lopes-Virella M.F. Antioxidized low density lipoprotein antibodies in patients with coronary heart disease and normal healthy volunteers.Int. J. Clin. Lab. Res. 1993; 23: 95-101Google Scholar, 9Palinski W. Ord V. Plump A.S. Breslow J.L. Steinberg D. Witztum J.L. ApoE-deficient mice are a model of lipoprotein oxidation in atherogenesis: demonstration of oxidation-specific epitopes in lesions and high titers of autoantibodies to malondialdehyde-lysine in serum.Arterioscler. Thromb. 1994; 14: 605-616Google Scholar, 10Palinski W. Tangirala R.K. Miller E. Young S.G. Witztum J.L. Increased autoantibody titers against epitopes of oxidized low density lipoprotein in LDL receptor-deficient mice with increased atherosclerosis.Arterioscler. Thromb. Vasc. Biol. 1995; 15: 1569-1576Google Scholar). This is particularly the case in the commonly used murine model of atherosclerosis, the apolipoprotein E-deficient (apoE−/−) mouse. The precise role of these autoantibodies in the pathogenesis of atherosclerosis is unknown for the most part. However, their involvement is strongly indicated by experiments in rabbits and mice involving immunization with OxLDL or malondialdehyde-modified LDL (MDA-LDL), which have demonstrated atheroprotection (11Palinski W. Miller E. Witztum J.L. Immunization of low density lipoprotein (LDL) receptor-deficient rabbits with homologous malondialdehyde-modified LDL reduces atherogenesis.Proc. Natl. Acad. Sci. USA. 1995; 92: 821-825Google Scholar, 12Ameli S. Hultgardh-Nilsson A. Regnstrom J. Calara F. Yano J. Cercek B. Shah P.K. Nilsson J. Effect of immunization with homologous LDL and oxidized LDL on early atherosclerosis in hypercholesterolemic rabbits.Arterioscler. Thromb. Vasc. Biol. 1996; 16: 1074-1079Google Scholar, 13Freigang S. Hörkkö S. Miller E. Witztum J.L. Palinski W. Immunization of LDL receptor-deficient mice with homologous malondialdehyde-modified and native LDL reduces progression of atherosclerosis by mechanisms other than induction of high titers of antibodies to oxidative neoepitopes.Arterioscler. Thromb. Vasc. Biol. 1998; 18: 1972-1982Google Scholar, 14George J. Afek A. Gilburd B. Levkovitz H. Shaish A. Goldberg I. Kopolovic Y. Wick G. Shoenfeld Y. Harats D. Hyperimmunization of apoE-deficient mice with homologous malondialdehyde low-density lipoprotein early 1998; Scholar, G. A. LDL immunization T cell antibody formation and against atherosclerosis.Arterioscler. Thromb. Vasc. Biol. 2001; Scholar). Although the by which such immunization atheroprotection is mechanism be the of enhanced clearance of early of OxLDL from the such modified from the wall. in in which LDL was injected into rabbits that high antibody titers to LDL, such enhanced plasma clearance was demonstrated Witztum J.L. Carew T.E. R.C. Steinberg D. and of degradation of low density lipoprotein in normal and rabbits.J. Res. Scholar). the other atherogenesis in hypercholesterolemic mice, to a extent in some in the of complete immune deficiency T and B a role in atherosclerotic formation in the apolipoprotein E-deficient Natl. Acad. Sci. USA. 1997; Scholar, C.A. V. Y. J. J. Getz G.S. The of immune deficiency on and atherosclerosis in Thromb. Vasc. Biol. 2001; Scholar, are in early Clin. 2001; Scholar), a in which antibody formation is Because of the to epitopes of OxLDL in mice, it was possible to a of autoantibodies from the of these mice that to epitopes of OxLDL W. Hörkkö S. Miller E. Witztum J.L. of antibodies to epitopes of oxidized from apolipoprotein E-deficient mice. of epitopes of oxidized low density lipoprotein in human Clin. 1996; Scholar). In of autoantibodies was such as the antibody which the and which was to bind to the of oxidized such as in OxLDL Hörkkö S. Palinski W. Witztum J.L. antibodies with the may in atherosclerosis, and Clin. 2000; Scholar). However, EO6 not bind to the of as in native LDL, they the such as be used to the in plasma of OxLDL oxidized phospholipid (OxPL) In we have taken of the complete of mice to autoantibodies to OxLDL epitopes a role in the of of for to promote enhanced clearance of OxLDL from the circulation. modified of which not with scavenger immune with such to enhanced clearance receptors on such a mechanism a major to the in vivo clearance of that of OxLDL in plasma of immune-deficient animals be increased with of immune-competent and that the plasma clearance of OxLDL be in the immune-deficient of these was in of immune-deficient and immune-competent mice. LDL was from human plasma by The and of in human Clin. Scholar). The plasma was to and the LDL was against and copper OxLDL as W. Ord V. Plump A.S. Breslow J.L. Steinberg D. Witztum J.L. ApoE-deficient mice are a model of lipoprotein oxidation in atherogenesis: demonstration of oxidation-specific epitopes in lesions and high titers of autoantibodies to malondialdehyde-lysine in serum.Arterioscler. Thromb. 1994; 14: 605-616Google with the LDL was extensively against to the It was to of LDL of and with copper for these the was and the OxLDL against to the copper by with the Biol. Chem. and mice and mice in both and C.A. V. Y. J. J. Getz G.S. The of immune deficiency on and atherosclerosis in Thromb. Vasc. Biol. 2001; mice to mice for or on or a of cholesterol and for of The was may the difference in the rate of clearance of the injected human LDL (hLDL) the immune-competent and mice. cholesterol from on a by In study mice with and a was the injected the with or of LDL taken and and the In study mice and injected with of copper OxLDL and and and and In both the was from the to that used for In all was to the and plasma was and on the mice in with of and plasma for autoantibody the of oxidation epitopes of LDL, and immune to the injected LDL by S. Miller E. Palinski W. Witztum J.L. The epitopes for some antibodies are of oxidized phospholipid and other Natl. Acad. Sci. USA. 1997; Scholar). by and and the of the plasma a in and autoantibodies and with in and was with and was to by of in the for in a plasma was in and results are as the of hLDL in the a murine antibody for human apoB-100 S.G. Witztum J.L. S. of the low density lipoprotein of B. by a Scholar), was to a of in the with with all by the of for The and of murine in was to for It was in experiments that the not the of to bind apoB-100 these the of hLDL bound to apoB-100 was to for by of the with and the of in and plasma was in and results are as The of OxPL epitopes on the LDL was the antibody EO6 W. Hörkkö S. Miller E. Witztum J.L. of antibodies to epitopes of oxidized from apolipoprotein E-deficient mice. of epitopes of oxidized low density lipoprotein in human Clin. 1996; that was EO6 was and in The of OxPL apoB-100 a of was as the of EO6 by the of This a of OxPL apoB-100 OxPL epitopes on the endogenous murine the antibody E. Young S.G. of antibodies for apolipoprotein in apolipoprotein Res. Scholar), for was used to the a E. Young S.G. of antibodies for apolipoprotein in apolipoprotein Res. antibody to a of murine apoB-100 was used for as and by The of apoB-100 was in a to that used for the EO6 of human immune associated with the human apoB-100 was as was and was detected as the murine on the of the the from and used for to was used for which was in experiments not to bind to the by the than the The mice with mice to mice that mature T and B cells C.A. V. Y. J. J. Getz G.S. The of immune deficiency on and atherosclerosis in Thromb. Vasc. Biol. 2001; Scholar). and mice on or on a for a of cholesterol the of the a which plasma cholesterol are greatly that both the and the mice on the and greatly increased plasma cholesterol Although we not the cholesterol for the mice are for a of animals cholesterol of and apolipoprotein plasma cholesterol in the mice on the and in mice on are in a apolipoprotein plasma cholesterol in the mice on the and in mice on are that mice in plasma we examined the plasma of a of the mice used in study for the of antibodies to mice not any with and against was in the plasma of all the immune-competent mice. the oxidation of a LDL and its clearance from the we injected native hLDL into immune-competent and mice or a The of a antibody that human apoB-100 to hLDL as a it is possible to the hLDL from plasma into mice Miller E. G. H. Witztum J.L. A.J. mice increased lipoprotein oxidation and Biol. Chem. 2000; Scholar). was and the of human apoB-100 in plasma was The the of human apoB-100 in all of that of hLDL injected into In all of the mice, there was a of human apoB-100 from the that by there was of the injected hLDL in the plasma. Because these animals are for the LDL clearance is and is to the clearance by Miller E. G. H. Witztum J.L. A.J. mice increased lipoprotein oxidation and Biol. Chem. 2000; Scholar). hLDL is not as by the murine LDL the is a major for the clearance of hLDL Y. J. receptor low-density lipoprotein uptake by the liver but no on cholesterol or in the Natl. Acad. Sci. USA. 1995; 92: Scholar). mechanisms to for a of the the mice clearance of the injected hLDL with the clearance in immune-competent mice. However, the was both and the immune-deficient animals the for cleared the hLDL to a greater extent than the immune-competent animals This was also for the animals on the of of hLDL into mice, but results of of hLDL and such experiments in mice and in mice to mice for not LDL of the is which is within the are by such as the antibody that from the of mice W. Hörkkö S. Miller E. Witztum J.L. of antibodies to epitopes of oxidized from apolipoprotein E-deficient mice. of epitopes of oxidized low density lipoprotein in human Clin. 1996; Scholar). the injected hLDL such in the we the hLDL in the plasma and used EO6 to the of on the hLDL There was a in EO6 apoB-100 and the mice on or a or they immune or immune there was difference the of immune status. we immune the injected hLDL and endogenous murine into immune-competent mice. This was by the of murine and bound to the as in with the hLDL in all immune-competent mice and the of these immune increased with of LDL. This that the bound most of the injected LDL that with of circulation. that these are as bound LDL and thus represent the of bound to the hLDL over immune formation with the hLDL was in the mice with the mice. The recognition of OxLDL by scavenger receptors a high of modification of the LDL. the of modification of apoB-100 that in modified LDL, the LDL is LDL receptor and is of to and by the LDL receptor F. Witztum J.L. that and modified Thromb. Vasc. Biol. 1997; Scholar). the of modification on the injected native hLDL in the experiments is and such hLDL is on the extent of of LDL also to immune clearance is not It is that it is not to extensively modified LDL in the of we that the not have a of immune deficiency on LDL of the extent of LDL modification that to the injected we but of native hLDL we injected hLDL that extensively oxidized vivo the of OxLDL was and to be extensively modified, as demonstrated by on and by a greatly increased of EO6 not human OxLDL injected into mice on the The clearance of the injected human OxLDL was by with is of the of OxLDL the is extensively and demonstrated the of to bind the OxLDL in as as in the murine plasma also the EO6 on the Because of the clearance of we experiments in mice with injected human OxLDL and that the of these experiments be from to by which of the injected cleared from the by the of human apoB-100 or EO6 the human OxLDL was injected into the murine we with the immune-competent mice, the clearance of the human apoB-100 was in the in the immune-deficient mice However, the of the clearance was in immune-deficient and immune-competent mice. Because the EO6 faster than that of the human the a from to in plasma over in both immune-competent and mice of these is that the human OxLDL injected there is in the of oxidation and that the most oxidized are cleared in the immune-competent mice. these suggest that in there was difference by immune status. that the results of these experiments is the transfer of OxPL from the injected hLDL to the endogenous LDL. to a it the of the the of human the extent of antibody which to murine apoB-100 and not to human apoB-100 E. Young S.G. of antibodies for apolipoprotein in apolipoprotein Res. Scholar). EO6 associated with the apoB-100 was Although there was a of transfer of oxidized lipid to murine LDL the in there was no difference in the extent of transfer of oxidized lipid to the endogenous LDL as a function of immune status. is by proinflammatory mechanisms and by the of and immune responses. In hypercholesterolemic there is a to oxidation-specific epitopes of OxLDL that the of atherosclerosis W. Ord V. Plump A.S. Breslow J.L. Steinberg D. Witztum J.L. ApoE-deficient mice are a model of lipoprotein oxidation in atherogenesis: demonstration of oxidation-specific epitopes in lesions and high titers of autoantibodies to malondialdehyde-lysine in serum.Arterioscler. Thromb. 1994; 14: 605-616Google Scholar, 10Palinski W. Tangirala R.K. Miller E. Young S.G. Witztum J.L. Increased autoantibody titers against epitopes of oxidized low density lipoprotein in LDL receptor-deficient mice with increased atherosclerosis.Arterioscler. Thromb. Vasc. Biol. 1995; 15: 1569-1576Google Scholar). The that immune modulate atherogenesis is from the numerous now that immunization of hypercholesterolemic animals with OxLDL with of oxidation-specific epitopes on such as to of the progression of disease (11Palinski W. Miller E. Witztum J.L. Immunization of low density lipoprotein (LDL) receptor-deficient rabbits with homologous malondialdehyde-modified LDL reduces atherogenesis.Proc. Natl. Acad. Sci. USA. 1995; 92: 821-825Google Scholar, 12Ameli S. Hultgardh-Nilsson A. Regnstrom J. Calara F. Yano J. Cercek B. Shah P.K. Nilsson J. Effect of immunization with homologous LDL and oxidized LDL on early atherosclerosis in hypercholesterolemic rabbits.Arterioscler. Thromb. Vasc. Biol. 1996; 16: 1074-1079Google Scholar, 13Freigang S. Hörkkö S. Miller E. Witztum J.L. Palinski W. Immunization of LDL receptor-deficient mice with homologous malondialdehyde-modified and native LDL reduces progression of atherosclerosis by mechanisms other than induction of high titers of antibodies to oxidative neoepitopes.Arterioscler. Thromb. Vasc. Biol. 1998; 18: 1972-1982Google Scholar, 14George J. Afek A. Gilburd B. Levkovitz H. Shaish A. Goldberg I. Kopolovic Y. Wick G. Shoenfeld Y. Harats D. Hyperimmunization of apoE-deficient mice with homologous malondialdehyde low-density lipoprotein early 1998; Scholar, G. A. LDL immunization T cell antibody formation and against atherosclerosis.Arterioscler. Thromb. Vasc. Biol. 2001; Scholar). However, the by which mechanism by which high autoantibody titers to OxLDL epitopes be is by to of enhanced to in such as and thus oxidized from the wall. of such enhanced plasma clearance was by the demonstration that there was enhanced plasma clearance of LDL in rabbits with LDL and that the LDL was to the and from the Witztum J.L. Carew T.E. R.C. Steinberg D. and of degradation of low density lipoprotein in normal and rabbits.J. Res. Scholar). In the we used a to the clearance of LDL in mice. In of Miller E. G. H. Witztum J.L. A.J. mice increased lipoprotein oxidation and Biol. Chem. 2000; Scholar, Y. J. receptor low-density lipoprotein uptake by the liver but no on cholesterol or in the Natl. Acad. Sci. USA. 1995; 92: Scholar), we the plasma clearance of hLDL in mice. there was a progressive of OxPL epitopes on the LDL its in the circulation. It is from these the progressive of OxPL on LDL de novo oxidation that as the LDL or it the transfer LDL of oxidized from other such as other or cells or which we have to such epitopes Witztum J.L. The of antibodies for and Scholar). In it is of that we a progressive in EO6 epitopes over on the hLDL injected into hypercholesterolemic mice in we any such in LDL injected into hypercholesterolemic LDL receptor-deficient mice, the of the hLDL in these mice was greatly not of hLDL into LDL receptor-deficient mice, than of the injected lipoprotein from the plasma and the lipoprotein was oxidized was with for that there is a increased of oxidation in the mice J. Increased plasma and lipoprotein lipid in apoE-deficient Res. 1994; Scholar, R.K. D. S. K. E. of and of atherosclerosis by apolipoprotein Biol. Chem. 2001; Scholar). The of may for the rate of of EO6 on hLDL in mice with the of in LDL receptor-deficient mice. In we injected hLDL into mice that high titers of autoantibodies to as by antibodies. hypothesis was that as the hLDL modified, it bind the and in the clearance of the modified LDL from plasma. we that the hLDL have enhanced rate of clearance in the immune-competent mice with the mice, which such antibodies. In to that the clearance of the modified LDL by mechanisms to any role in the of LDL from plasma. The clearance of the injected LDL a variety of the LDL receptor is for the clearance of the of the native LDL, of to the of Y. J. receptor low-density lipoprotein uptake by the liver but no on cholesterol or in the Natl. Acad. Sci. USA. 1995; 92: Scholar). The extent of modification of the of injected hLDL is not to be in and of to scavenger we the that a of modified to have such enhanced that we was that of of such modified as a of and as the hLDL it of in the immune-competent mice and the or of these immune on the rate of LDL suggesting that these immune not a major role in the of the modified hLDL the we that in the immune-deficient mice there was accelerated of human apoB-100 from the plasma. The mechanism that for is not all is that the formation of immune with LDL in the plasma of immune-competent mice modified hLDL in the plasma its normal In the we the of hLDL in which a of the It be that the of modification was to to enhanced plasma we extensively OxLDL by with extensively modified OxPL epitopes by EO6 in both the lipid and bound to the apoB-100 and up to of oxidized bound to the apoB-100 S. Miller E. H. G. Palinski W. Witztum J.L. autoantibodies for oxidized or oxidized phospholipid macrophage uptake of oxidized low-density Clin. Scholar). such a modified LDL to enhanced clearance injected into the immune-competent mice clearance was the rate of clearance of the as by human apoB-100 was accelerated with the clearance of native of scavenger clearance of extensively modified LDL However, we not any difference in the rate of clearance of the human apoB-100 of OxLDL the immune-competent and mice. also the rate of clearance of the OxPL detected by EO6 LDL that over there is a decrease in the This was for there is up to of oxidized bound to apoB-100 in such and have the to as the apoB-100 was cleared from plasma. The in over is with the in the of EO6 to apoB-100 be with the of clearance of the some oxidized than and these most to the of in clearance mechanisms the most extensively modified lipoprotein particles. This is with the of scavenger receptors with OxLDL A. K. Hörkkö S. W. Steinberg D. V. Witztum J.L. oxidized LDL, and Y. Acad. Sci. 2001; Scholar). to the in the be that a of the EO6 in the OxLDL that is in the lipid S. Miller E. H. G. Palinski W. Witztum J.L. autoantibodies for oxidized or oxidized phospholipid macrophage uptake of oxidized low-density Clin. is the OxLDL to other and other we used the to the endogenous murine apoB-100 in the plasma in there was a in the of OxPL murine apoB-100 the of the human by a as these murine The of the and of the OxPL on murine apoB-100 in to the of OxPL from human apoB-100 a the of the EO6 from the injected human OxLDL and its in the murine apoB-100 particles. However, the of OxPL detected on the murine apoB-100 was that the in the injected human OxLDL was and the in the murine apoB-100 was a of the of the injected human OxLDL and of the murine apoB-100 we that such transfer for no than a of the OxPL that plasma associated with the human OxLDL. these the for transfer of some of the OxPL on OxLDL to other lipoprotein and we that a greater was to other Although the rate of clearance of the OxLDL in the immune-competent and mice was not a of the a difference in the of OxLDL the mice. was in the particularly the but was in the immune-deficient possible are that immune clearance may a role in the of the most extensively OxLDL or that the of scavenger receptors may be in immune-deficient mice of the of immune cells such the of clearance There are possible for the of a in the apoB-100 in the plasma of animals injected with native LDL The injected LDL may be in the in OxPL may be to the injected LDL from endogenous or cells of the mouse. Because hLDL is by the murine LDL modified LDL is cleared than native LDL, by the LDL receptor or by other clearance which of these the major role in for of of oxidation the modified LDL is not by scavenger the other we oxidized hLDL we the the most OxLDL appeared to be cleared than the oxidized particles. It is that scavenger receptors are in There may be a of the clearance of the most OxLDL in the immune-deficient animals the but the for is as In of the of native hLDL and oxidized hLDL in mice, immune or immune of clearance of or OxLDL from the plasma. The also that the clearance mechanisms are to the extent of oxidative study a model for the in vivo study of the of modified the as a Although for the of antibodies to oxidation epitopes as clearance mechanisms for the of plasma LDL, they the role of oxidation of in the of atherogenesis or the possible of immune taken up the receptor on macrophages in the formation of lesion foam In addition, some autoantibodies to oxidation epitopes may the of atherogenesis by the uptake by macrophages of OxLDL Hörkkö S. A. Palinski W. Witztum J.L. atherosclerotic lesion and oxidized Scholar). the of OxLDL with its antibodies within the vessel wall be of great This was by of of in and and was by a from the apolipoprotein human LDL malondialdehyde-modified LDL oxidized LDL oxidized phospholipid
Reardon et al. (Tue,) studied this question.