ApoC-III content of apoB-containing lipoproteins is associated with binding to the vascular proteoglycan biglycan
Retention of apolipoprotein (apo)B and apoE-containing lipoproteins by extracellular vascular proteoglycans is critical in atherogenesis. Moreover, high circulating apoC-III levels are associated with increased atherosclerosis risk. To test whether apoC-III content of apoB-containing lipoproteins affects their ability to bind to the vascular proteoglycan biglycan, we evaluated the impact of apoC-III on the interaction of [35S]SO4-biglycan derived from cultured arterial smooth muscle cells with lipoproteins obtained from individuals across a spectrum of lipid concentrations. The extent of biglycan binding correlated positively with apoC-III levels within VLDL (r = 0.78, P < 0.01), IDL (r = 0.67, P < 0.01), and LDL (r = 0.52, P < 0.05). Moreover, the biglycan binding of VLDL, IDL, and LDL was reduced after depletion of apoC-III-containing lipoprotein particles in plasma by anti-apoC-III immunoaffinity chromatography. Since apoC-III does not bind biglycan directly, enhanced biglycan binding may result from a conformational change associated with increased apo C-III content by which apoB and/or apoE become more accessible to proteoglycans. This may be an intrinsic property of lipoproteins, since exogenous apoC-III enrichment of LDL and VLDL did not increase binding.ApoC-III content may thus be a marker for lipoproteins characterized as having an increased ability to bind proteoglycans. Retention of apolipoprotein (apo)B and apoE-containing lipoproteins by extracellular vascular proteoglycans is critical in atherogenesis. Moreover, high circulating apoC-III levels are associated with increased atherosclerosis risk. To test whether apoC-III content of apoB-containing lipoproteins affects their ability to bind to the vascular proteoglycan biglycan, we evaluated the impact of apoC-III on the interaction of [35S]SO4-biglycan derived from cultured arterial smooth muscle cells with lipoproteins obtained from individuals across a spectrum of lipid concentrations. The extent of biglycan binding correlated positively with apoC-III levels within VLDL (r = 0.78, P < 0.01), IDL (r = 0.67, P < 0.01), and LDL (r = 0.52, P < 0.05). Moreover, the biglycan binding of VLDL, IDL, and LDL was reduced after depletion of apoC-III-containing lipoprotein particles in plasma by anti-apoC-III immunoaffinity chromatography. Since apoC-III does not bind biglycan directly, enhanced biglycan binding may result from a conformational change associated with increased apo C-III content by which apoB and/or apoE become more accessible to proteoglycans. This may be an intrinsic property of lipoproteins, since exogenous apoC-III enrichment of LDL and VLDL did not increase binding. ApoC-III content may thus be a marker for lipoproteins characterized as having an increased ability to bind proteoglycans. A critical step in the pathogenesis of atherosclerosis is the deposition and retention of lipoproteins by vascular extracellular matrix molecules, particularly proteoglycans (1Hollander W. Unified concept on the role of acid mucopolysaccharides and connective tissue proteins in the accumulation of lipids, lipoproteins, and calcium in the atherosclerotic plaque.Exp. Mol. Pathol. 1976; 25: 106-120Google Scholar, 2Camejo G. The interaction of lipids and lipoproteins with the intercellular matrix of arterial tissue: its possible role in atherogenesis.Adv. Lipid Res. 1982; 19: 1-53Google Scholar, 3Berenson G.S. Radhakrishnamurthy B. Srinivasan S.R. Vijayagopal P. Dalferes E.R. Proteoglycans and potential mechanisms related to atherosclerosis.Ann. N. Y. Acad. Sci. 1985; 454: 69-78Google Scholar, 4Williams K.J. Tabas I. The response-to-retention hypothesis of early atherogenesis.Arterioscler. Thromb. Vasc. Biol. 1995; 15: 551-561Google Scholar). Arterial wall proteoglycans play a key role in the development of atherosclerosis by interaction of negatively charged groups on their glycosaminoglycan side chains with clusters of positively charged residues on apolipoproteins (apo)B and apoE (5Camejo G. Olofsson S-O. Lopez F. Carlsson P. Bondjers G. Identification of apoB-100 segments mediating the interaction of low density lipoproteins with arterial proteoglycans.Arteriosclerosis. 1988; 8: 368-377Google Scholar, 6Camejo G. Rosengren B. Olson U. Lopez F. Olofson S.O. Westerlund C. Bondjers G. Molecular basis of the association of arterial proteoglycans with low density lipoproteins: Its effect on the structure of the lipoprotein particle.Eur. Heart J. 1990; 11: 164-173Google Scholar, 7Hurt-Camejo E. Olsson U. Wiklund O. Bondjers G. Camejo G. Cellular consequences of the association of apoB lipoproteins with proteoglycans. Potential contribution to atherogenesis.Arterioscler. Thromb. Vasc. Biol. 1997; 17: 1011-1017Google Scholar). Kinetic analyses suggest that the trapping of lipoproteins by arterial wall proteoglycans is due to selective retention rather than increased delivery of the lipoproteins (4Williams K.J. Tabas I. The response-to-retention hypothesis of early atherogenesis.Arterioscler. Thromb. Vasc. Biol. 1995; 15: 551-561Google Scholar, 8Schwenke D.C. Carew T.E. Initiation of atherosclerotic lesions in cholesterol-fed rabbits.Arteriosclerosis. 1989; 9: 908-918Google Scholar). Thus, it is important to understand the factors that mediate the binding of lipoproteins to proteoglycans. High concentrations of apoC-III in plasma and on apoB-containing lipoproteins are associated with increased cardiovascular disease risk (9Hodis H.N. Mack W.J. Triglyceride-rich lipoproteins and the progression of coronary artery disease.Curr. Opin. Lipidol. 1995; 6: 209-214Google Scholar, 10Gervaise N. Garrigue M.A. Lasfargues G. Lecomte P. Triglycerides, apoC3 and Lp B:C3 and cardiovascular risk in type II diabetes.Diabetologia. 2000; 43: 703-708Google Scholar, 11Sacks 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: 1886-1892Google Scholar). However, unlike apoB and apoE, apoC-III lacks clusters of positively charged amino acid residues (12Brewer Jr., H.B. Shulman R. Herbert P. Ronan R. Wehrly K. The complete amino acid sequence of alanine apolipoprotein (apoC-3), and apolipoprotein from human plasma very low density lipoproteins.J. Biol. Chem. 1974; 249: 4975-4984Google Scholar) and thus does not contain any putative heparin or proteoglycan binding regions. Consistent with this we have shown that apoE-free HDL, which contain abundant apoC-III, do not bind to proteoglycans(13O'Brien K.D. Olin K.L. Alpers C.E. Chiu W. Ferguson M. Hudkins K. Wight T.N. Chait A. Comparison of apolipoprotein and proteoglycan deposits in human coronary atherosclerotic plaques: colocalization of biglycan with apolipoproteins.Circulation. 1998; 98: 519-527Google Scholar, 14Olin K.L. Potter-Perigo S. Barrett P.H. Wight T.N. Chait A. Biglycan, a vascular proteoglycan, binds differently to HDL(2) and HDL(3): role of apoE.Arterioscler. Thromb. Vasc. Biol. 2001; 21: 129-135Google Scholar), thus further indicating that apoC-III does not bind directly to proteoglycans. The cardiovascular risk associated with high levels of apoC-III is thought to relate, in part, to its association with elevated triglyceride concentrations that are due to apoC-III-mediated impairment of lipolysis (15Batal R. Tremblay M. Barrett P.H. Jacques H. Fredenrich A. Mamer O. Davignon J. Cohn J.S. Plasma kinetics of apoC-III and apoE in normolipidemic and hypertriglyceridemic subjects.J. Lipid Res. 2000; 41: 706-718Google Scholar, 16Jong M.C. Havekes L.M. Insights into apolipoprotein C metabolism from transgenic and gene-targeted mice.Int. J. Tissue React. 2000; 22: 59-66Google Scholar). However, several investigators have reported that the presence of apoC-III on lipoproteins may affect the accessibility of apoB and/or apoE for the low density lipoprotein receptor (LDLR) (16Jong M.C. Havekes L.M. Insights into apolipoprotein C metabolism from transgenic and gene-targeted mice.Int. J. Tissue React. 2000; 22: 59-66Google Scholar, 17Aalto-Setälä K. Fisher E.A. Chen X. Chajek-Shaul T. Hayek T. Zechner R. Walsh A. Ramakrishnan R. Ginsberg H.N. Breslow J.L. Mechanism of hypertriglyceridemia in human apolipoprotein (Apo) CIII transgenic mice.J. Clin. Invest. 1992; 90: 1889-1900Google Scholar, 18Clavey V. Lestavel-Delattre S. Copin C. Bard J.M. Fruchart J.C. Modulation of lipoprotein B binding to the LDL receptor by exogenous lipids and apolipoproteins CI, CII, CIII, and E.Arterioscler. Thromb. Vasc. Biol. 1995; 15: 963-971Google Scholar, 19Liu H. Talmud P.J. Lins L. Brasseur R. Olivecrona G. Peelman F. Vandekerckhove J. Rosseneu M. Labeur C. Characterization of recombinant wild type and site-directed mutations of apolipoprotein C-III: lipid binding, displacement of ApoE, and inhibition of lipoprotein lipase.Biochemistry. 2000; 39: 9201-9212Google Scholar). In addition, VLDL from apo-CIII transgenic mice was found to bind less well to heparin Sepharose to VLDL from which result in reduced of VLDL to lipoprotein and in lipolysis (16Jong M.C. Havekes L.M. Insights into apolipoprotein C metabolism from transgenic and gene-targeted mice.Int. J. Tissue React. 2000; 22: 59-66Google Scholar, Hayek T. T. Walsh A. Ramakrishnan R. Ginsberg H.N. Breslow J.L. of apolipoprotein hypertriglyceridemia in transgenic mice.J. Clin. Invest. Scholar). Thus, may be in which apoC-III affects lipoprotein metabolism and atherogenesis. Since lipoproteins with the and proteoglycans we that the presence of apoC-III on lipoproteins affect lipoproteins with proteoglycans. we whether the content of apoC-III on apoB-containing lipoproteins IDL, and their ability to bind to the extracellular vascular proteoglycan evaluated lipoprotein binding to biglycan biglycan to play an role in the trapping and retention of lipoproteins, as it was found to with apoB and apoE in human atherosclerotic lesions K.D. Olin K.L. Alpers C.E. Chiu W. Ferguson M. Hudkins K. Wight T.N. Chait A. Comparison of apolipoprotein and proteoglycan deposits in human coronary atherosclerotic plaques: colocalization of biglycan with apolipoproteins.Circulation. 1998; 98: 519-527Google Scholar). plasma obtained after an from = with a of lipid not on any to lipid metabolism and of the their to in this which was by the for of the of was by into of and a LDL = was by from VLDL and IDL = from of the of LDL by density as in of the F. L. R. N. and of the low density Scholar, M. in content of low density lipoproteins associated with low density lipoprotein Lipid Res. 1990; triglyceride and and LDL LDL = in a = of apoB-containing lipoproteins was on plasma and lipoprotein and in Plasma Scholar). lipoproteins with and the with and of on the of of on of lipoprotein of for in the IDL and LDL was within of LDL was within and as and and triglyceride to the a in Biol. Chem. Scholar) and a Chem. LDL concentrations by a of the of with the Biol. Chem. Scholar) as the apoE, and apoC-III with from and Chem. for and Lipid of lipoproteins was in as L. H. Chait A. of low density lipoprotein by arterial smooth muscle Clin. Invest. Scholar). of the lipoproteins, as and density and as M.C. of lipoprotein by Lipid Res. 1992; Scholar, M. P.J. of low density lipoprotein Lipid Res. 1997; Scholar). in a of and was from to and a apoC-III by plasma with apoC-III to in a as an and of apoC-III, was from the by the matrix with of The to the plasma IDL, and from and plasma by as The and of and and and Scholar). is important to that this apoC-III-containing and not To test exogenous apoC-III to lipoproteins result in increased biglycan binding, levels of apoC-III to VLDL or LDL as N. J. Fruchart J.C. V. P. of apolipoprotein C-III on the binding of lipoproteins to the Biol. Chem. 1997; Scholar). [35S]SO4-biglycan was derived from cultured human arterial smooth muscle as K.L. Potter-Perigo S. Barrett Wight T.N. Chait A. the binding of low density lipoproteins to and biglycan by cultured arterial smooth muscle Biol. Chem. Scholar). the was on in and with and and to a Sepharose in and and 1982; Scholar). was for biglycan, and into the for the was by a the of biglycan sequence of proteoglycan with proteoglycan and several tissue proteins in a of Biol. Chem. 1989; Scholar) from of and enhanced with The ability of lipoprotein lipoproteins or LDL to bind biglycan was a of the by Camejo K.L. Potter-Perigo S. Barrett Wight T.N. Chait A. the binding of low density lipoproteins to and biglycan by cultured arterial smooth muscle Biol. Chem. Scholar, G. G. Rosengren B. E. Bondjers G. of low density lipoproteins by proteoglycans by and human arterial smooth muscle Biol. Chem. Scholar, E. Camejo G. P. of interaction by Mol. Biol. 1998; Scholar). of this are that the interaction step is and and and that for the binding be to the the [35S]SO4-biglycan and lipoprotein with and concentrations of the lipoproteins with a of biglycan in a of of A for of to the and to in on and in for The in in for and to for or a for [35S]SO4-biglycan to lipoprotein into the and/or the biglycan to the binding to [35S]SO4-biglycan was by the with The of biglycan in was a II and the for of lipoprotein to was for interaction II binding was evaluated by the of biglycan that binds to a of for binding and by and of was by and P < LDL was from VLDL and IDL from of individuals VLDL and IDL did not contain a of to in the of this it be that with concentrations of lipoprotein and a of [35S]SO4-biglycan in is an of [35S]SO4-biglycan the and a of [35S]SO4-biglycan the which is biglycan for the that VLDL, IDL, and LDL biglycan with of are with the that is of binding for the interaction of apolipoproteins and proteoglycans (5Camejo G. Olofsson S-O. Lopez F. Carlsson P. Bondjers G. Identification of apoB-100 segments mediating the interaction of low density lipoproteins with arterial proteoglycans.Arteriosclerosis. 1988; 8: 368-377Google Scholar). The extent of biglycan binding was evaluated in the biglycan that to and lipoprotein was for the binding interaction of LDL the ability to bind biglycan, by IDL and VLDL In addition, we that within an biglycan binding to the LDL was than to the suggest that the density of lipoproteins was related to their for In addition, the density of the lipoproteins and LDL correlated with their and density (r = P < for be that the the the more positively charged the Thus, with M. P.J. of low density lipoprotein Lipid Res. 1997; Scholar), a density is related to its that VLDL was the positively charged by IDL and the of biglycan that to the lipoproteins was correlated with and density (r = P < for are with the that the interaction lipoproteins and proteoglycans is in that lipoproteins with bind to negatively charged glycosaminoglycan side chains on proteoglycans G. Rosengren B. Olson U. Lopez F. Olofson S.O. Westerlund C. Bondjers G. Molecular basis of the association of arterial proteoglycans with low density lipoproteins: Its effect on the structure of the lipoprotein particle.Eur. Heart J. 1990; 11: 164-173Google Scholar, 7Hurt-Camejo E. Olsson U. Wiklund O. Bondjers G. Camejo G. Cellular consequences of the association of apoB lipoproteins with proteoglycans. Potential contribution to atherogenesis.Arterioscler. Thromb. Vasc. Biol. 1997; 17: 1011-1017Google Scholar, Molecular of 1989; 9: of lipoproteins = = = in a binds to biglycan with high of a from the is concentrations of VLDL, IDL, and LDL from a with a of biglycan for to in as in and that binds lipoproteins the or a into the [35S]SO4-biglycan to the of the The binding for the interaction of VLDL IDL and LDL and biglycan that shown in A. The of [35S]SO4-biglycan for was and the of for that lipoprotein The the as a are from a that is of lipoprotein from and binding for the interaction of lipoproteins with = = = [35S]SO4-biglycan to = = = = for LDL P < for in a a P < for lipoprotein the of biglycan was found to be related to apoC-III content A was found and the of apoC-III lipoprotein Thus, within of the lipoprotein IDL, and we that the the apoC-III the the ability of the lipoprotein to bind the extracellular arterial proteoglycan biglycan in that apoC-III content a role in lipoprotein binding. LDL was correlated with the apoC-III content (r = P = In the LDL particles a of apoC-III lipoprotein the of apoC-III with the for the interaction of the lipoprotein with are shown to the of a apoC-III content with the from the interaction with biglycan IDL, the with a of biglycan for to in as in and The role of apoC-III in mediating the interaction of lipoproteins with biglycan was further in VLDL, IDL, and LDL from plasma that was of apoC-III-containing particles by an apoC-III lipoprotein biglycan binding was reduced after the plasma from which the lipoprotein was of apoC-III-containing particles the biglycan binding for lipoproteins and after apoC-III VLDL the by IDL and LDL This the for the of apoC-III in the lipoproteins, with VLDL the content of apoC-III, by IDL and LDL by in the of lipoprotein from plasma and after it the apoC-III not binding of biglycan to lipoproteins that contain apoC-III to are shown for the interaction of biglycan and apoC-III-containing VLDL, IDL, and LDL or VLDL, IDL, and LDL from the plasma that an apoC-III of lipoprotein particles with a of biglycan for to in as in and The the as The are from a that is of binding of biglycan to lipoproteins that contain apoC-III to are shown for the interaction of biglycan and apoC-III-containing VLDL, IDL, and LDL or VLDL, IDL, and LDL from the plasma that an apoC-III of lipoprotein particles with a of biglycan for to in as in and The the as The are from a that is of The of the of apoB and apoE in VLDL and LDL was found to positively with the of biglycan to of lipoproteins (r = and P < 0.05). Thus, not the of apolipoproteins to contain proteoglycan binding apoB and Molecular of 1989; 9: Scholar) is associated with an increased ability of a lipoprotein to bind However, the extent of lipoprotein binding to biglycan and lipoprotein content of apoE, or not To binding of lipoproteins to biglycan be by the on lipoproteins, we evaluated the lipoprotein lipoprotein binding, and apoC-III of the lipoprotein evaluated apoC-III content was positively associated with lipoprotein potential and (r = P < This be since VLDL the of apoC-III and is the negatively charged of LDL was a density and apoC-III content (r = P = was association apoC-III content and density for VLDL and IDL not In addition, lipoprotein from plasma that of apoC-III-containing particles by immunoaffinity to lipoprotein from apoC-III-containing plasma not further hypothesis that apoC-III is not directly to mediate binding, since lipoproteins with the apoC-III content have the density and the the and of biglycan binding. the apoC-III-mediated enhanced binding of lipoproteins to biglycan was not related to as by and ApoC-III is on lipoprotein and a role in lipid metabolism (15Batal R. Tremblay M. Barrett P.H. Jacques H. Fredenrich A. Mamer O. Davignon J. Cohn J.S. Plasma kinetics of apoC-III and apoE in normolipidemic and hypertriglyceridemic subjects.J. Lipid Res. 2000; 41: 706-718Google Scholar, J.C. Ginsberg H.N. of plasma apolipoprotein and C-III concentrations in very low density and high density lipoproteins: for the of the of lipoproteins.J. Lipid Res. 1988; Scholar). However, high levels of apoC-III on apoB-containing lipoproteins and in plasma are risk factors for cardiovascular disease in individuals (9Hodis H.N. Mack W.J. Triglyceride-rich lipoproteins and the progression of coronary artery disease.Curr. Opin. Lipidol. 1995; 6: 209-214Google Scholar, 10Gervaise N. Garrigue M.A. Lasfargues G. Lecomte P. Triglycerides, apoC3 and Lp B:C3 and cardiovascular risk in type II diabetes.Diabetologia. 2000; 43: 703-708Google Scholar, 11Sacks 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: 1886-1892Google Scholar). In apoC-III is associated with is of apoC-III to VLDL and a increase in plasma levels of apoC-III in hypertriglyceridemia (15Batal R. Tremblay M. Barrett P.H. Jacques H. Fredenrich A. Mamer O. Davignon J. Cohn J.S. Plasma kinetics of apoC-III and apoE in normolipidemic and hypertriglyceridemic subjects.J. Lipid Res. 2000; 41: 706-718Google Scholar, of J. 1998; Scholar). Since high apoC-III levels are associated with in lipoprotein and the of apoB and on lipoproteins X. C-III displacement of apolipoprotein from effect of Lipid Res. Scholar), we whether the content of apoC-III was important in mediating the interaction of VLDL, IDL, and LDL with extracellular arterial proteoglycans. to biglycan it to play an role in the trapping and retention of lipoproteins K.D. Olin K.L. Alpers C.E. Chiu W. Ferguson M. Hudkins K. Wight T.N. Chait A. Comparison of apolipoprotein and proteoglycan deposits in human coronary atherosclerotic plaques: colocalization of biglycan with apolipoproteins.Circulation. 1998; 98: 519-527Google Scholar). intrinsic apoC-III content was found to be associated with biglycan binding for of the lipoprotein the that apoC-III does not bind to biglycan of apoC-III on the lipoprotein particles may for the that the of biglycan binding for VLDL and IDL with apoC-III content by which A role for apoC-III in the binding of lipoproteins to biglycan was further evaluated in in which we biglycan binding to lipoproteins and after apoC-III-containing particles from plasma by immunoaffinity chromatography. VLDL less to biglycan than apoC-III-containing IDL and LDL an ability to bind biglycan and the effect of apoC-III-containing particles from lipoproteins was not as as found for In apoC-III was to lipoproteins in this exogenous did not result in increased biglycan binding, rather it by not Thus, the from further the that it is the intrinsic apoC-III content that is associated with the ability of lipoproteins to bind that the content of apoB apoE on VLDL and LDL affect the to which lipoproteins bind This is with the presence of binding on apoB and apoE (5Camejo G. Olofsson S-O. Lopez F. Carlsson P. Bondjers G. Identification of apoB-100 segments mediating the interaction of low density lipoproteins with arterial proteoglycans.Arteriosclerosis. 1988; 8: 368-377Google Scholar, Molecular of 1989; 9: Scholar). However, we that the of apoC-III on a lipoprotein was an of its ability to bind This is since apoC-III does not contain any binding does it have clusters of positively charged amino acid residues and that as binding for the negatively charged glycosaminoglycan side chains on proteoglycans (12Brewer Jr., H.B. Shulman R. Herbert P. Ronan R. Wehrly K. The complete amino acid sequence of alanine apolipoprotein (apoC-3), and apolipoprotein from human plasma very low density lipoproteins.J. Biol. Chem. 1974; 249: 4975-4984Google Scholar). of suggest that apoC-III is not directly in the binding of lipoproteins to VLDL as apoC-III as for a of biglycan binding is for VLDL and we have that apoE-free does not bind to biglycan K.D. Olin K.L. Alpers C.E. Chiu W. Ferguson M. Hudkins K. Wight T.N. Chait A. Comparison of apolipoprotein and proteoglycan deposits in human coronary atherosclerotic plaques: colocalization of biglycan with apolipoproteins.Circulation. 1998; 98: 519-527Google Scholar), high apoC-III is possible that apoC-III, in its within lipoproteins, is by a conformational change in lipoproteins, the accessibility of apoB and/or to proteoglycan binding. a conformational change may not be by apoC-III, may an intrinsic property of the that affects proteoglycan binding and apoC-III In to for proteoglycan binding, lipoproteins have reported to have a for the (16Jong M.C. Havekes L.M. Insights into apolipoprotein C metabolism from transgenic and gene-targeted mice.Int. J. Tissue React. 2000; 22: 59-66Google Scholar, 17Aalto-Setälä K. Fisher E.A. Chen X. Chajek-Shaul T. Hayek T. Zechner R. Walsh A. Ramakrishnan R. Ginsberg H.N. Breslow J.L. Mechanism of hypertriglyceridemia in human apolipoprotein (Apo) CIII transgenic mice.J. Clin. Invest. 1992; 90: 1889-1900Google Scholar, 18Clavey V. Lestavel-Delattre S. Copin C. Bard J.M. Fruchart J.C. Modulation of lipoprotein B binding to the LDL receptor by exogenous lipids and apolipoproteins CI, CII, CIII, and E.Arterioscler. Thromb. Vasc. Biol. 1995; 15: 963-971Google Scholar). The of the interaction of apolipoproteins with the is to that are However, in mice or human that amino acid in the putative binding on apoB in reduced binding of LDL to vascular not to the J. Olin K. I. Chait A. Wight T.N. Identification of the in A in apolipoprotein affects proteoglycan interaction LDL receptor Clin. Invest. 1998; Scholar), that are in the binding of apolipoproteins to proteoglycans and the The in the association of apoC-III content with and proteoglycan binding may be of lipoprotein with the and proteoglycans are not the that apoC-III affects the ability of lipoproteins to with the and extracellular of which in the metabolism of apoB-containing lipoproteins K.J. by which lipoprotein of low density and lipoproteins.J. Biol. Chem. 1992; Scholar, lipoprotein key proteoglycans and apolipoprotein Lipid Res. Scholar). that in human as an elevated a low and a high increase its for proteoglycans E. Camejo G. Rosengren B. Lopez F. Wiklund O. Bondjers G. of of low density lipoprotein by human Lipid Res. 1990; Scholar, G. Camejo Olsson U. Bondjers G. Proteoglycans and lipoproteins in Opin. Lipidol. Scholar). 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J. of plasma lipid and on the interaction low density lipoprotein with human arterial wall Scholar). we we an effect of on biglycan binding, that the biglycan than In addition, LDL have a content of apoC-III and a as by and density to with high apoC-III levels have a of high circulating as well as having a of LDL and lipoproteins, of which we are associated with an enhanced for arterial proteoglycans. this may individuals a risk of The of from the the with increased binding to extracellular vascular as biglycan, that lipoproteins be particularly This may in the increased risk of cardiovascular disease that is in with high plasma levels of This was in by of and and a of the Heart