Rapid turnover of apolipoprotein C-III-containing triglyceride-rich lipoproteins contributing to the formation of LDL subfractions

Abstract

The atherogenicity theory for triglyceride-rich lipoproteins (TRLs; VLDL + intermediate density lipoprotein) generally cites the action of apolipoprotein C-III (apoC-III), a component of some TRLs, to retard their metabolism in plasma. We studied the kinetics of multiple TRL and LDL subfractions according to the content of apoC-III and apoE in 11 hypertriglyceridemic and normolipidemic persons. The liver secretes mainly two types of apoB lipoproteins: TRL with apoC-III and LDL without apoC-III. Approximately 45% of TRLs with apoC-III are secreted together with apoE. Contrary to expectation, TRLs with apoC-III but not apoE have fast catabolism, losing some or all of their apoC-III and becoming LDL. In contrast, apoE directs TRL flux toward rapid clearance, limiting LDL formation. Direct clearance of TRL with apoC-III is suppressed among particles also containing apoE. TRLs without apoC-III or apoE are a minor, slow-metabolizing precursor of LDL with little direct removal. Increased VLDL apoC-III levels are correlated with increased VLDL production rather than with slow particle turnover. Finally, hypertriglyceridemic subjects have significantly greater production of apoC-III-containing VLDL and global prolongation in residence time of all particle types. ApoE may be the key determinant of the metabolic fate of atherogenic apoC-III-containing TRLs in plasma, channeling them toward removal from the circulation and reducing the formation of LDLs, both those with apoC-III and the main type without apoC-III. The atherogenicity theory for triglyceride-rich lipoproteins (TRLs; VLDL + intermediate density lipoprotein) generally cites the action of apolipoprotein C-III (apoC-III), a component of some TRLs, to retard their metabolism in plasma. We studied the kinetics of multiple TRL and LDL subfractions according to the content of apoC-III and apoE in 11 hypertriglyceridemic and normolipidemic persons. The liver secretes mainly two types of apoB lipoproteins: TRL with apoC-III and LDL without apoC-III. Approximately 45% of TRLs with apoC-III are secreted together with apoE. Contrary to expectation, TRLs with apoC-III but not apoE have fast catabolism, losing some or all of their apoC-III and becoming LDL. In contrast, apoE directs TRL flux toward rapid clearance, limiting LDL formation. Direct clearance of TRL with apoC-III is suppressed among particles also containing apoE. TRLs without apoC-III or apoE are a minor, slow-metabolizing precursor of LDL with little direct removal. Increased VLDL apoC-III levels are correlated with increased VLDL production rather than with slow particle turnover. Finally, hypertriglyceridemic subjects have significantly greater production of apoC-III-containing VLDL and global prolongation in residence time of all particle types. ApoE may be the key determinant of the metabolic fate of atherogenic apoC-III-containing TRLs in plasma, channeling them toward removal from the circulation and reducing the formation of LDLs, both those with apoC-III and the main type without apoC-III. Epidemiological studies demonstrate that apolipoprotein C-III (apoC-III) and the apoB lipoproteins that have apoC-III as a component independently predict coronary heart disease (1Alaupovic P. Mack W.J. Knight-Gibson C. Hodis H.N. The role of triglyceride-rich lipoprotein families in the progression of atherosclerotic lesions as determined by sequential coronary angiography from a controlled clinical trial..Arterioscler. Thromb. Vasc. Biol. 1997; 17: 715-722Crossref PubMed Scopus (161) Google Scholar, 2Sacks F.M. Alaupovic P. Moye L.A. Cole T.G. Sussex B. Stampfer M.J. Pfeffer M.A. Braunwald E. VLDL, apolipoproteins B, CIII, and E, and risk of recurrent coronary events in the Cholesterol and Recurrent Events (CARE) Trial..Circulation. 2000; 102: 1886-1892Crossref PubMed Scopus (415) Google Scholar, 3Lee S.J. Campos H. Moye L.A. Sacks F.M. LDL containing apolipoprotein CIII is an independent risk factor for coronary events in diabetic patients..Arterioscler. Thromb. Vasc. Biol. 2003; 23: 853-858Crossref PubMed Scopus (149) Google Scholar). ApoC-III is present on ∼40–80% of triglyceride-rich lipoproteins (TRLs) and ∼5–10% of LDLs in plasma P. of apolipoproteins for and of plasma PubMed Google Scholar, H. C. Sacks F.M. of lipoproteins with apoB by of apoE or apoC-III in and PubMed Google Scholar, C. Campos H. H. Sacks F.M. of on the lipoprotein particle by apolipoproteins and C-III PubMed Google Scholar). The by apoC-III and are in that apoC-III lipoprotein of lipoprotein by an of density PubMed Scopus Google Scholar, W.J. Alaupovic P. of lipoprotein by of apolipoprotein PubMed Scopus Google and C. of and from density lipoproteins on plasma PubMed Scopus Google and retard the clearance of VLDL by with the of C. of lipoprotein to the LDL by and apolipoproteins CIII, and Thromb. Vasc. Biol. PubMed Scopus Google or apoE to The lipoprotein of that the of lipoproteins containing and Biol. PubMed Google Scholar, E. of by apolipoprotein of apolipoprotein metabolism of triglyceride-rich lipoproteins the density lipoprotein Biol. PubMed Google Scholar). Direct a role of apoC-III in TRL metabolism from of apoC-III in as a of CIII in PubMed Scopus Google Scholar, H.N. of in apolipoprotein CIII density lipoprotein with increased CIII and on the PubMed Scopus Google Scholar, of the metabolic of triglyceride-rich lipoproteins from and apoC-III PubMed Google Scholar, S.J. of apolipoprotein C-III in in an of apolipoprotein that is by apolipoprotein Biol. PubMed Google Scholar, to apolipoprotein CIII in apolipoprotein is not by on apolipoprotein 1997; PubMed Scopus Google apoC-III H. P. of the apolipoprotein C-III in in and from Biol. PubMed Google Scholar, H. C-III by lipoprotein in and apoE PubMed Google Scholar). In particle clearance LDL H.N. of in apolipoprotein CIII density lipoprotein with increased CIII and on the PubMed Scopus Google Scholar, of the metabolic of triglyceride-rich lipoproteins from and apoC-III PubMed Google Scholar, S.J. of apolipoprotein C-III in in an of apolipoprotein that is by apolipoprotein Biol. PubMed Google to of the metabolic of triglyceride-rich lipoproteins from and apoC-III PubMed Google Scholar, to apolipoprotein CIII in apolipoprotein is not by on apolipoprotein 1997; PubMed Scopus Google of to apolipoprotein CIII in apolipoprotein is not by on apolipoprotein 1997; PubMed Scopus Google Scholar, H. C-III by lipoprotein in and apoE PubMed Google and of VLDL H.N. of in apolipoprotein CIII density lipoprotein with increased CIII and on the PubMed Scopus Google Scholar, S.J. of apolipoprotein C-III in in an of apolipoprotein that is by apolipoprotein Biol. PubMed Google have all as for the hypertriglyceridemic of apoC-III. In is also for apoC-III TRL with of apoC-III and rapid VLDL clearance H.N. P. metabolism in subjects with of apolipoproteins CIII and that apolipoprotein CIII of triglyceride-rich lipoproteins by lipoprotein in PubMed Scopus Google Scholar). In a the plasma and of VLDL apoC-III correlated with those of VLDL of production of plasma and lipoprotein apolipoprotein C-III is to the and of production of VLDL in subjects with and levels of PubMed Scopus Google Scholar). In in a of VLDL apoC-III and correlated with VLDL and VLDL apoB residence but not with C-III and as of lipoprotein and apolipoprotein Thromb. Vasc. Biol. PubMed Scopus Google Scholar). in and studies all that apoC-III the metabolism of the studies not a are The that levels of apoC-III by VLDL to a theory for the atherogenicity of by apoC-III of TRL the residence for TRLs and their atherogenic the theory for LDL LDL residence and of to is direct that apoC-III-containing TRLs, the particles that predict coronary heart have residence in plasma. In to the of apoE in the clearance of apoB lipoproteins by to of apolipoproteins and on lipoprotein to density lipoprotein Biol. PubMed Google Scholar, than a 2000; PubMed Scopus Google and role for apolipoprotein in lipoprotein metabolism Biol. PubMed Google Scholar). of apoE in the by the of apoC-III S.J. of apolipoprotein C-III in in an of apolipoprotein that is by apolipoprotein Biol. PubMed Google Scholar). are in or are for a of have metabolism of TRL and TRL L.A. in metabolism of lipoproteins in apoE PubMed Scopus Google Scholar, L.A. apolipoprotein PubMed Scopus Google Scholar). apoC-III and apoE may be as in apoB lipoprotein The of the is to in as as apoB lipoprotein on the types of particles that are for and that are to lipoprotein metabolism and atherogenic is to apoC-III-containing apoB on lipoprotein metabolism of apoC-III and apoE are not the of apoC-III and apoE on the TRL particle an to the of the role of as in a H. Sacks F.M. metabolism of VLDL according to content of apoE and Thromb. Vasc. Biol. PubMed Scopus Google Scholar). to the of apoC-III and apoE on the metabolism of apoB and from plasma apoB lipoprotein types with apoC-III or both of or of clinical from two of the apoB of TRLs that have apoC-III is an risk factor for the of plasma S.J. Campos H. Moye L.A. Sacks F.M. LDL containing apolipoprotein CIII is an independent risk factor for coronary events in diabetic patients..Arterioscler. Thromb. Vasc. Biol. 2003; 23: 853-858Crossref PubMed Scopus (149) Google Scholar). that apoC-III by and as a component of TRL and LDL is in by in and and by P. P. Sacks F.M. CIII of in and of PubMed Scopus Google Scholar, P. P. Sacks F.M. CIII in apolipoprotein lipoproteins the of to PubMed Scopus Google Scholar, P. Sacks F.M. to and Thromb. Vasc. Biol. PubMed Scopus Google Scholar). for of the that or of apoB lipoproteins with apoC-III. hypertriglyceridemic and normolipidemic the and or and the of that The by the the of and and of the and apolipoproteins the two the two density lipoprotein the two the two the two the two the two apolipoprotein B. are in the an density of density of density of the two the two in a apolipoprotein B. are in the an density of density of density of a controlled the The to the as and not to or of levels to of or and to in that The the metabolic of the and The of from from from and from from and from to the of and in the an a of by a of for of also the in the the and the to a and that or and that of the for to and the metabolic of a and by for in and of lipoproteins by apoE and apoC-III content with apoE and apoC-III to as H. C. Sacks F.M. of lipoproteins with apoB by of apoE or apoC-III in and PubMed Google Scholar, C. Campos H. H. Sacks F.M. of on the lipoprotein particle by apolipoproteins and C-III PubMed Google Scholar). with and the by The by with and and and from the with sequential plasma those with both apoE and apoC-III those with apoE but not apoC-III those with apoC-III but not apoE and those without apoE or apoC-III The of the as the of or that is from plasma by the is for apoC-III and for apoE. In of and on the in and of or apoB in the that of apoE or apoC-III from apoB lipoproteins or not or particles to or We also the of and for the and and for and and for the and plasma of apoB lipoproteins in the and of plasma not the The on a in an to VLDL of VLDL intermediate density lipoprotein and a of the of and The and of and and Scholar). density of as the for LDL to by lipoprotein is and C. H. H. and of the plasma lipoprotein the PubMed Scopus Google Scholar). and determined on a and determined by of for and apolipoprotein and and of and apoB from the lipoproteins with and the of apolipoproteins than as determined by with and the to as H. Sacks F.M. metabolism of VLDL according to content of apoE and Thromb. Vasc. Biol. PubMed Scopus Google Scholar). on a and by the the the and the the with a of Campos H. H. Sacks F.M. of and of in of PubMed Scopus Google Scholar, C. P. B. of lipoprotein on kinetics of apolipoprotein in Google Scholar). apoB by and among the lipoprotein to their apoB for to be of and apoB in apoB lipoprotein density for to the to the the of the plasma is by a for the time for the and of plasma. The is by lipoprotein to a for VLDL a and an to apoB lipoproteins without apoE and apoC-III 11 and are and of VLDL, is for VLDL, is for and are for and to apoB to and to in and are to are not of and in VLDL, intermediate density lipoprotein and LDL subfractions in normolipidemic and hypertriglyceridemic apolipoprotein lipoproteins with both apoE and particles with apoC-III but not particles with apoE but not apoC-III of LDL to and not particles without apoE or apoC-III. and in to the are on a for and are in the of and in VLDL, intermediate density lipoprotein and LDL subfractions in normolipidemic and hypertriglyceridemic apolipoprotein lipoproteins with both apoE and particles with apoC-III but not particles with apoE but not apoC-III of LDL to and not particles without apoE or apoC-III. and in to the are on a for and are in the of and in VLDL, intermediate density lipoprotein and LDL subfractions in normolipidemic and hypertriglyceridemic apolipoprotein lipoproteins with both apoE and particles with apoC-III but not particles with apoE but not apoC-III of LDL to and not particles without apoE or apoC-III. and in to the are on a for and are in the a for the production and of plasma of density of density of density of for The direct and direct removal of apoB and of lipoprotein The among apoB lipoproteins of the apoE and apoC-III VLDL for to and are also and to be a in the for the of is among apoB lipoproteins of apoE and apoC-III VLDL plasma apoB lipoproteins their apoE and apoC-III content P. of apolipoproteins for and of plasma PubMed Google a of apoE and apoC-III. a TRL particle apoC-III or apoE on the of apoE and the apoB lipoproteins of apoC-III or apoE with or apoB may apoC-III or apoE and also their with apoE and apoC-III the of the and to that a that are with the are to the by and are to the for are or are particle and content are also a the by the and of all 11 to the and for both and in a and by the for and for a of is to to and for both and of apoB is also and the are in the The of for and those for the the and are as for and a for and also to the and VLDL and of lipoproteins for the are in and normolipidemic have and The of them are but not of plasma and LDL are in the two The hypertriglyceridemic have significantly of plasma VLDL VLDL and VLDL and of for particle and for LDL subfractions are The of VLDL particles are secreted as apoC-III-containing in both hypertriglyceridemic and normolipidemic VLDL without apoE or apoC-III of VLDL In the secreted as to in normolipidemic subjects and in hypertriglyceridemic the are secreted as The is in secreted without apoC-III. Approximately of TRLs that are secreted with apoC-III also apoE In contrast, all of the apoB lipoproteins secreted with apoE have apoC-III. than of TRLs are secreted with apoE but not apoC-III in both to of apoB lipoproteins and is TRLs of VLDL of than of LDL is secreted with apoE. apoB lipoproteins have of of than their without apoC-III the of the the is and the of is for apoC-III-containing are for all 11 apoC-III-containing VLDL, and LDL have fast than those without apoC-III of and TRL and all significantly than those of are generally not from as the of apoE and apoC-III to flux In both hypertriglyceridemic and normolipidemic a of VLDL and is from apoC-III-containing TRLs by of apoC-III from with the of to that not apoE or apoC-III are for direct removal and are to of is to to and the to and Approximately of TRLs are to LDL or LDL the are from the circulation as TRLs from TRLs to LDLs is a for LDL formation in plasma. TRLs are for than of plasma LDLs among hypertriglyceridemic as LDL as direct liver are in the In the of LDLs are also to In TRLs and LDLs of the production of of in hypertriglyceridemic and normolipidemic apoB lipoprotein by apoC-III and apoE content and by of the liver direct liver to the the of liver of lipoprotein and direct the the of flux of and in the for are The is significantly in hypertriglyceridemic than in normolipidemic the is significantly in hypertriglyceridemic subjects of and direct liver to LDL formation. production of types of LDL particles from direct liver and in hypertriglyceridemic and normolipidemic in LDL production hypertriglyceridemic and normolipidemic for triglyceride-rich TRLs of liver of apoB the of particles are of TRLs the of apoC-III are to direct removal than to The for removal are in than for type of We not of LDL particles with apoE but not of the fast removal of of TRLs are from the circulation LDL are as VLDL or and some are to the of TRLs are The of TRLs to LDL formation is of plasma LDL with for TRLs two TRL particle types as for LDL with their for for among normolipidemic for direct removal for TRLs are intermediate and than but than apoE in TRL toward the direct removal as as apoC-III in LDL without apoE or apoC-III of LDL in the circulation are of TRL in plasma or are secreted from the the of to LDL significantly LDLs from TRL than from direct liver in hypertriglyceridemic subjects and in normolipidemic both LDLs by TRLs by the and in hypertriglyceridemic and normolipidemic by TRLs and and TRLs and LDL subfractions demonstrate metabolic than LDL that not have apoC-III. both and LDL subfractions have than their of and apoC-III circulation in plasma to to the metabolic fate of TRLs Finally, among both hypertriglyceridemic and of and are from the circulation or as a of the of apoE on LDL In contrast, of and are from the circulation of VLDL apoC-III and apoE are and with VLDL for apoC-III and for of apoC-III and apoE in VLDL are with the of VLDL apoB but not with the and VLDL particles that apoC-III with or without the of apoC-III particle is not with or for or clearance not that both apoC-III and the of apoE to apoB is significantly correlated with their in are with for direct removal in with H. C. Sacks F.M. of lipoproteins with apoB by of apoE or apoC-III in and PubMed Google is a toward a content of and particle among apoC-III-containing TRLs and LDLs with those without apoC-III the is that apoB lipoproteins with apoC-III significantly and particle than those without apoC-III. density apoB lipoproteins have the content of and by and have the In type of particle and are in VLDL, as particle density subjects have significantly than normolipidemic subjects in all VLDL and of their apoE and apoC-III that slow TRL in than apoC-III and apoE. subjects also have for some from TRLs to and LDLs in of apoC-III-containing TRLs in plasma and flux to may be to levels of among hypertriglyceridemic are significantly correlated with for levels and for the VLDL for the metabolic in is the of VLDL for apoB lipoproteins are in both is a in the of VLDL of apoB in hypertriglyceridemic than as as in normolipidemic subjects with increased of VLDL, hypertriglyceridemic subjects have a in the of VLDL the of slow metabolism of the of TRLs and of apoC-III-containing in significantly increased plasma levels of apoC-III-containing TRLs and LDLs among hypertriglyceridemic in TRL and LDL metabolism according to have apoC-III or apoE. particles VLDL metabolism in both hypertriglyceridemic and normolipidemic those with apoC-III apoE LDL lipoproteins containing apoC-III have rapid and than particles without apoC-III in both hypertriglyceridemic and normolipidemic of the that of apoC-III is a for a residence time in plasma for VLDL, or LDL. that the of apoC-III is with of direct removal of lipoproteins from the circulation and of their to and in contrast, the of flux in of direct removal. TRLs that not have apoC-III or a of TRL are to particles to LDLs, and is little direct removal from the circulation that LDLs from two plasma and that have apoC-III but not apoE and direct In are with some of apoC-III and apoE. VLDL, the with the to and LDL direct removal by or be to the action of apoC-III on particle clearance by of with the LDL or C. of lipoprotein to the LDL by and apolipoproteins CIII, and Thromb. Vasc. Biol. PubMed Scopus Google Scholar). VLDL the for particle clearance are and the for to and LDL are than those of VLDL, the role of apoE in clearance of apolipoproteins and on lipoprotein to density lipoprotein Biol. PubMed Google Scholar, than a 2000; PubMed Scopus Google Scholar). also that VLDL apoE the of apoE to is to for the direct removal of with apoC-III studies that of VLDL or in be by apoE or by apoE of the metabolic of triglyceride-rich lipoproteins from and apoC-III PubMed Google Scholar, S.J. of apolipoprotein C-III in in an of apolipoprotein that is by apolipoprotein Biol. PubMed Google Scholar). the of apoE the for direct removal among and also by is the of apoC-III is not with a metabolism of apoB We are that is for rapid for apoC-III-containing TRLs and LDLs is from the and is not a of of the all 11 the of for the the of fast and for apoC-III-containing fast of apoC-III-containing particles to those without apoC-III for all density the apoC-III-containing particles from plasma by that the apoC-III-containing particles are that their Finally, are the of in the studied a time and in of normolipidemic and studied on a with those from apoC-III studies and the of as the main in that apoC-III may be a direct for lipoprotein W.J. Alaupovic P. of lipoprotein by of apolipoprotein PubMed Scopus Google Scholar). is the in as apoC-III not have lipoprotein H.N. of in apolipoprotein CIII density lipoprotein with increased CIII and on the PubMed Scopus Google Scholar, S.J. of apolipoprotein C-III in in an of apolipoprotein that is by apolipoprotein Biol. PubMed Google Scholar, to apolipoprotein CIII in apolipoprotein is not by on apolipoprotein 1997; PubMed Scopus Google and TRLs from apoC-III not retard action in H.N. of in apolipoprotein CIII density lipoprotein with increased CIII and on the PubMed Scopus Google Scholar, S.J. of apolipoprotein C-III in in an of apolipoprotein that is by apolipoprotein Biol. PubMed Google Scholar). In of the of of apoC-III particle and the for among apoC-III-containing that from apoC-III may have to as for in of the metabolic of triglyceride-rich lipoproteins from and apoC-III PubMed Google Scholar, to apolipoprotein CIII in apolipoprotein is not by on apolipoprotein 1997; PubMed Scopus Google Scholar). to of VLDL apoC-III also the and be a for and clearance, as in In in apoC-III content of apoB lipoproteins in with increased to ApoC-III content of lipoproteins is with to the PubMed Scopus Google Scholar). from not a VLDL metabolism is by apoC-III with for a in apoC-III VLDL metabolism from lipoprotein from apoC-III have significantly of both apoE H.N. of in apolipoprotein CIII density lipoprotein with increased CIII and on the PubMed Scopus Google Scholar, of the metabolic of triglyceride-rich lipoproteins from and apoC-III PubMed Google Scholar, S.J. of apolipoprotein C-III in in an of apolipoprotein that is by apolipoprotein Biol. PubMed Google and H.N. of in apolipoprotein CIII density lipoprotein with increased CIII and on the PubMed Scopus Google Scholar, S.J. of apolipoprotein C-III in in an of apolipoprotein that is by apolipoprotein Biol. PubMed Google particle than those from apoC-III-containing TRLs and LDLs in in and studies H. Sacks F.M. metabolism of VLDL according to content of apoE and Thromb. Vasc. Biol. PubMed Scopus Google have of the of apolipoproteins by apoC-III in with the of of and apoE on TRLs in In the may be to the of and the levels of apoB lipoproteins to the of apoC-III in the the for the apoC-III and coronary heart that lipoproteins be in plasma, lipoproteins are as fast or than their and some be as The apoC-III and risk of coronary heart disease among studies (1Alaupovic P. Mack W.J. Knight-Gibson C. Hodis H.N. The role of triglyceride-rich lipoprotein families in the progression of atherosclerotic lesions as determined by sequential coronary angiography from a controlled clinical trial..Arterioscler. Thromb. Vasc. Biol. 1997; 17: 715-722Crossref PubMed Scopus (161) Google Scholar, 2Sacks F.M. Alaupovic P. Moye L.A. Cole T.G. Sussex B. Stampfer M.J. Pfeffer M.A. Braunwald E. VLDL, apolipoproteins B, CIII, and E, and risk of recurrent coronary events in the Cholesterol and Recurrent Events (CARE) Trial..Circulation. 2000; 102: 1886-1892Crossref PubMed Scopus (415) Google Scholar, 3Lee S.J. Campos H. Moye L.A. Sacks F.M. LDL containing apolipoprotein CIII is an independent risk factor for coronary events in diabetic patients..Arterioscler. Thromb. Vasc. Biol. 2003; 23: 853-858Crossref PubMed Scopus (149) Google may be to direct in We that apoC-III or as a component of VLDL and LDL the of to P. P. Sacks F.M. CIII of in and of PubMed Scopus Google Scholar, P. P. Sacks F.M. CIII in apolipoprotein lipoproteins the of to PubMed Scopus Google Scholar, P. Sacks F.M. to and Thromb. Vasc. Biol. PubMed Scopus Google Scholar). ApoC-III in and and in the of and all of have on in apoC-III may also the of apoB lipoproteins to ApoC-III content of lipoproteins is with to the PubMed Scopus Google an action that the of apoB lipoproteins in the the of apoC-III on TRLs may be a factor in their In to the content of their for LDL formation the apoB lipoproteins the atherogenic of a global in for TRLs in of particle apoC-III and apoE studies have slow VLDL among hypertriglyceridemic subjects L.A. P. The metabolism of apolipoprotein in subjects with and PubMed Google Scholar, P. of in a with PubMed Scopus Google Scholar). to the action of a apoC-III in hypertriglyceridemic subjects C-III and as of lipoprotein and apolipoprotein Thromb. Vasc. Biol. PubMed Scopus Google Scholar). also that is independently with TRL that than apoC-III or apoE retard TRL in also that hypertriglyceridemic subjects have a greater of VLDL particles containing apoC-III without apoE than normolipidemic VLDL apoC-III levels are correlated with both VLDL and VLDL but have with VLDL are with the that apoC-III may as a for of VLDL but not apoB in some apoC-III H.N. of in apolipoprotein CIII density lipoprotein with increased CIII and on the PubMed Scopus Google Scholar, S.J. of apolipoprotein C-III in in an of apolipoprotein that is by apolipoprotein Biol. PubMed Google Scholar). In production of VLDL apoC-III with the of VLDL of production of plasma and lipoprotein apolipoprotein C-III is to the and of production of VLDL in subjects with and levels of PubMed Scopus Google with the of is that apoC-III the of triglyceride-rich VLDL the and the for the in plasma of apoC-III or apoE by TRLs that not them the is a of plasma apoC-III and apoE is on and studies have that apoC-III and apoE VLDL and P. of for of for a of apoC-III in PubMed Scopus Google Scholar, of apolipoprotein metabolism in 23: PubMed Google Scholar). may of the of of apoC-III or apoE from or TRLs to TRLs the is with and be by as direct also not the or of apoC-III or apoE that among particles that not a the in the not the that from the In that apoE is to from to VLDL of apolipoprotein metabolism in 23: PubMed Google Scholar). the be to the of a the of VLDL to B. H. of a on apolipoprotein and metabolism in PubMed Scopus Google a that to the content of both apoE and apoC-III. of apoC-III and apoE kinetics have not to to are among apoB and apoB lipoproteins and with some of and in VLDL or and H. kinetics of apoC-III and apoE in normolipidemic and hypertriglyceridemic 2000; PubMed Google Scholar, H.N. for of apolipoprotein C-III in plasma PubMed Google and to a P. of for of for a of apoC-III in PubMed Scopus Google Scholar, of apolipoproteins and in subjects PubMed Scopus Google Scholar). apoC-III-containing have on of apoC-III the in the circulation of particles with those of and the of with of are with and not of apoC-III and apoE VLDL and that VLDL particles not apoC-III or the type of VLDL H. C. Sacks F.M. of lipoproteins with apoB by of apoE or apoC-III in and PubMed Google Scholar, C. Campos H. H. Sacks F.M. of on the lipoprotein particle by apolipoproteins and C-III PubMed Google not apoE circulation is by in that apoE not to apoB lipoproteins C. apolipoprotein E. of in the lipoprotein of the and Biol. PubMed Google Scholar). not VLDL are not apoE. apoE not to that are rapid the metabolic for VLDL ApoC-III but also from apoB lipoproteins and are by The of among apoB lipoproteins may on the of as for apoC-III and apoE. demonstrate and of from TRLs to may hypertriglyceridemic subjects in atherogenic apoB lipoproteins as a of the to particles to Finally, the of apoE and apoC-III from TRLs to may be a that apoB lipoprotein metabolism apoC-III and apoE are to with type and of metabolism than a 2000; PubMed Scopus Google Scholar, and C-III as of lipoprotein PubMed Scopus Google Scholar). In by of apoB lipoprotein metabolism to particle and apoC-III and apoE a for lipoprotein is lipoprotein that for and of for on that have both apoC-III and apoE. ApoC-III directs flux from direct removal by the liver to lipoproteins to and with apoC-III is from the particles on clearance, the of apoE the particles to the liver for the liver apoB lipoproteins with apoC-III that not also have particles that are not atherogenic but also for LDL. from the of VLDL with apoC-III but not to not but also and also for to the of an component of TRLs that is of coronary heart The are to the in The also to and for their and by and from the and of with