Analysis of Intimal Proteoglycans in Atherosclerosis-prone and Atherosclerosis-resistant Human Arteries by Mass Spectrometry

The propensity to develop atherosclerosis varies markedly among different sites in the human vasculature. To determine a possible cause for such differences in atherosclerosis susceptibility, a proteomics-based approach was used to assess the extracellular proteoglycan core protein composition of intimal hyperplasia from both the atherosclerosis-prone internal carotid artery and the atherosclerosis-resistant internal thoracic artery. The intimal proteoglycan composition in these preatherosclerotic lesions was found to be more complex than previously appreciated with up to eight distinct core proteins present, including the large extracellular proteoglycans versican and aggrecan, the basement membrane proteoglycan perlecan, the class I small leucine-rich proteoglycans biglycan and decorin, and the class II small leucine-rich proteoglycans lumican, fibromodulin, and prolargin/PRELP (proline arginine-rich end leucine-rich repeat protein). Although most of these proteoglycans seem to be present in similar amounts at the two locations, there was a selective enhanced deposition of lumican in the intima of the atherosclerosis-prone internal carotid artery compared with the intima of the atherosclerosis-resistant internal thoracic artery. The enhanced deposition of lumican in the intima of an atherosclerosis prone artery has important implications for the pathogenesis of atherosclerosis. The propensity to develop atherosclerosis varies markedly among different sites in the human vasculature. To determine a possible cause for such differences in atherosclerosis susceptibility, a proteomics-based approach was used to assess the extracellular proteoglycan core protein composition of intimal hyperplasia from both the atherosclerosis-prone internal carotid artery and the atherosclerosis-resistant internal thoracic artery. The intimal proteoglycan composition in these preatherosclerotic lesions was found to be more complex than previously appreciated with up to eight distinct core proteins present, including the large extracellular proteoglycans versican and aggrecan, the basement membrane proteoglycan perlecan, the class I small leucine-rich proteoglycans biglycan and decorin, and the class II small leucine-rich proteoglycans lumican, fibromodulin, and prolargin/PRELP (proline arginine-rich end leucine-rich repeat protein). Although most of these proteoglycans seem to be present in similar amounts at the two locations, there was a selective enhanced deposition of lumican in the intima of the atherosclerosis-prone internal carotid artery compared with the intima of the atherosclerosis-resistant internal thoracic artery. The enhanced deposition of lumican in the intima of an atherosclerosis prone artery has important implications for the pathogenesis of atherosclerosis. An important unexplained observation concerning atherosclerosis is the marked variability in susceptibility of different sites in the human vasculature to the development of the disease. For example, whereas the internal carotid and coronary arteries show marked susceptibility to the development of atherosclerosis, the internal thoracic and distal ulnar arteries are markedly resistant to it, despite routinely forming intimal hyperplasia (1Vink A. Schoneveld A.H. Poppen M. de Kleijn D.P.V. Borst C. Pasterkamp G. Morphometric and immunohistochemical characterization of the intimal layer throughout the arterial system of elderly humans.J. Anat. 2002; 200: 97-103Google Scholar, 2Ruengsakulrach P. Sinclair R. Komeda M. Raman J. Gordon I. Buxton B. Comparative histopathology of radial artery versus internal thoracic artery and risk factors for development of intimal hyperplasia and atherosclerosis.Circulation. 1999; 100: II-139-II-144Google Scholar, 3Fishbein M.C. Hartman G. Pathology of internal mammary arteries used as bypass grafts.Cardiovasc. Pathol. 1997; 6: 31-33Google Scholar, 4Stone J.R. Intimal hyperplasia in the distal ulnar artery: influence of gender and implications for the hypothenar hammer syndrome.Cardiovasc. Pathol. 2004; 13: 20-25Google Scholar, 5Wright I. The microscopical appearances of human peripheral arteries during growth and aging.J. Clin. Pathol. 1963; 16: 499-522Google Scholar). In humans, atherosclerotic lesions develop at sites of intimal hyperplasia or intimal thickening, and such lesions are regarded as precursor lesions for atherosclerosis (6Schwartz S.M. deBlois D. O’Brien E.R.M. The intima: soil for atherosclerosis and restenosis.Circ. Res. 1995; 77: 445-465Google Scholar, 7Stary H.C. Blankenhorn D.H. Chandler A.B. Glagov S. Insull W. Richardson M. Rosenfeld M.E. Schaffer S.A. Schwartz C.J. Wagner W.D. Wissler R.W. A definition of the intima of human arteries and of its atherosclerosis-prone regions.Circulation. 1992; 85: 391-405Google Scholar). Altered shear stresses distal to vascular branch points are likely to be responsible for the formation of much of the intimal hyperplasia in the human vasculature, and such altered shear forces are a plausible explanation for the characteristic eccentric appearance of intimal hyperplasia at these sites (8Davies P.F. Flow-mediated endothelial mechanotransduction.Physiol. Rev. 1995; 75: 519-560Google Scholar, 9Garcia-Cardena G. Comander J. Anderson K.R. Blackman B.R. Gimbrone M.A. Biomechanical activation of vascular endothelium as a determinant of its functional phenotype.Proc. Natl. Acad. Sci. U. S. A. 2001; 98: 4478-4485Google Scholar, 10Traub O. Berk B.C. Laminar shear stress: Mechanisms by which endothelial cells transduce an atheroprotective force.Arterioscler. Thromb. Vasc. Biol. 1998; 18: 677-685Google Scholar). However, there is currently no sufficient explanation for why such intimal hyperplasia will routinely progress to atherosclerosis at some locations, but not others, in the vasculature. Intimal proteoglycans are up-regulated at sites of intimal hyperplasia and seem to play a direct role in the development of atherosclerosis by binding and retaining apolipoprotein-B containing lipoproteins in the vessel wall and by regulating vascular cell growth (11Skålén K. Gustafsson M. Rydberg E.K. Hultén L.M. Wiklund O. Innerarity T.L. Borén J. Subendothelial retention of atherogenic lipoproteins in early atherosclerosis.Nature. 2002; 417: 750-754Google Scholar, 12Williams K.J. Arterial wall chondroitin sulfate proteoglycans: diverse molecules with distinct roles in lipoprotein retention and atherogenesis.Curr. Opin. Lipidol. 2001; 12: 477-487Google Scholar, 13Camejo G. Hurt-Camejo E. Wiklund O. Bondjers G. Association of apo B lipoproteins with arterial proteoglycans: pathological significance and molecular basis.Atherosclerosis. 1998; 139: 205-222Google Scholar, 14Williams K.J. Tabas I. The response-to-retention hypothesis of early atherogenesis.Arterioscler. Thromb. Vasc. Biol. 1995; 15: 551-561Google Scholar, 15Wight T.N. Merrilees M.J. Proteoglycans in atherosclerosis and restenosis, key roles for versican.Circ. Res. 2004; 94: 1158-1167Google Scholar). The lipoproteins sequestered in the intima probably stimulate a chronic inflammatory response, resulting in the accumulation of macrophages and the development of a necrotic/lipid core (16Becker A.E. de Boer O.J. van der Wal A.C. The role of inflammation and infection in coronary artery disease.Annu. Rev. Med. 2001; 52: 289-297Google Scholar, 17Libby P. Inflammation in atherosclerosis.Nature. 2002; 420: 868-874Google Scholar, 18Glass C.K. Witztum J.L. Atherosclerosis: the road ahead.Cell. 2001; 104: 503-516Google Scholar). Because proteoglycans deposited in intimal hyperplasia are believed to play a central role in the development of atherosclerosis, it was hypothesized that differences in the intimal extracellular proteoglycan composition may be at least partly responsible for the marked variation in susceptibility to atherosclerosis among different sites in the vasculature. Our previous understanding of the extracellular proteoglycan composition of human vascular intima has been relatively limited. Biglycan was definitively demonstrated in human intima by protein sequencing (19Stöcker G. Meyer H.E. Wagener C. Greiling H. Purification and N-terminal amino acid sequence of a chondroitin sulphate/dermatan sulphate proteoglycan isolated from intima/media preparations of human aorta.Biochem. J. 1991; 274: 415-420Google Scholar). In addition, immunologic and/or mRNA transcript analyses have provided evidence for additional proteoglycans in human intima, predominantly versican, decorin, perlecan, and lumican (20Gutierrez P. O’Brien K.D. Ferguson M. Nikkari S.T. Alpers C.E. Wight T.N. Differences in the distribution of versican, decorin, and biglycan in atherosclerotic human coronary arteries.Cardiovasc. Pathol. 1997; 6: 271-278Google Scholar, 21Kolodgie F.D. Burke A.P. Farb A. Weber D.K. Kutys R. Wight T.N. Virmani R. Differential accumulation of proteoglycans and hyaluronan in culprit lesions: insights into plaque erosion.Arterioscler. Thromb. Vasc. Biol. 2002; 22: 1642-1648Google Scholar, 22Lin H. Kanda T. Hoshino Y. Takase S.-I. Kobayashi I. Nagai R. McManus B.M. Versican, biglycan, and decorin protein expression patterns in coronary arteries: analysis of primary and restenotic lesions.Cardiovasc. Pathol. 1998; 7: 31-37Google Scholar, 23O’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, 24Onda M. Ishiwata T. Kawahara K. Wang R. Naito Z. Sugisaki Y. Expression of lumican in thickened intima and smooth muscle cells in human coronary atherosclerosis.Exp. Mol. Pathol. 2002; 72: 142-149Google Scholar, 25Chung I.-M. Gold H.K. Schwartz S.M. Ikari Y. Reidy M.A. Wight T.N. Enhanced extracellular matrix accumulation in restenosis of coronary arteries after stent deployment.J. Am. Col. Cardiol. 2002; 40: 2072-2081Google Scholar, 26Murdoch A.D. Iozzo R.V. Perlecan: the multidomain heparan sulphate proteoglycan of basement membrane and extracellular matrix.Virchows Archiv. A. Pathol. Anat. 1993; 423: 237-242Google Scholar). It is noteworthy that these immunohistochemical analyses have indicated that versican, biglycan, and lumican are present in both atherosclerotic lesions and preatherosclerotic intimal hyperplasia. In contrast, immunoreactivity for decorin has been reported to be present in atherosclerotic lesions but absent in intimal hyperplasia (20Gutierrez P. O’Brien K.D. Ferguson M. Nikkari S.T. Alpers C.E. Wight T.N. Differences in the distribution of versican, decorin, and biglycan in atherosclerotic human coronary arteries.Cardiovasc. Pathol. 1997; 6: 271-278Google Scholar). To gain a more complete understanding of the extracellular proteoglycan core protein composition of human vascular intima and how this composition may vary at different sites in the circulation, a proteomics-based approach was performed using both the atherosclerosis-prone internal carotid artery and the atherosclerosis-resistant internal thoracic artery. This analysis revealed that the extracellular proteoglycan core protein composition of human intimal hyperplasia is substantially more complex than previously realized. Furthermore, these studies have revealed that there is enhanced deposition of the class II small leucine-rich proteoglycan lumican in the intima of the atherosclerosis-prone internal carotid artery. Arterial segments were obtained from autopsies performed at Massachusetts General Hospital within 24 h of death from patients ranging in age from the 4th to 10th decades of life. Cases were excluded if there was a history of prior surgery or radiation therapy involving the arterial segments. The Hospital’s Human Subjects Institutional Review Board approved all activities. The left internal carotid artery at the level of the carotid bifurcation and the internal thoracic arteries at the level of the bifurcation of the intercostal arteries below the second rib were carefully identified and removed. A representative cross-section was fixed in 10% buffered formalin for 16 h, processed with paraffin embedding, and used to generate hematoxylin-and-eosin-stained histological slides. The of the was at for For this an atherosclerotic was as the of cells or a necrotic/lipid which II lesions and H.C. Chandler A.B. Glagov S. J.R. Insull W. Rosenfeld M.E. Schaffer S.A. Schwartz C.J. Wagner W.D. Wissler R.W. A definition of and lesions of atherosclerosis.Circulation. Scholar). For this intimal hyperplasia was as an intima than with or with an intimal of than were Morphometric analyses were performed using a with a with and analyses for the and for were performed using the after with was used at and was used at were identified as cells for The of macrophages present in an arterial was by with a and The of macrophages present was by the intimal by were in and and The thickened intima was carefully and with a The of the intimal was by histological To for the of the internal carotid both segments of internal thoracic artery from a were processed The intimal were with of A containing complete and for h at the were at for to the of the were for protein using the To the was of The was at with for The and proteoglycans were by for at The was in a and with the by of of the by for at with by with B A with an additional by with and and two with B. The proteoglycans were from the by the of of containing and by for at of the proteoglycans were into a which was fixed with 10% and with containing the proteoglycans were to and the were and by by as in previously J.R. J.L. T. and sites of in Scholar). were obtained a in the in the of at obtained was used to the human protein using The was using no and a precursor of for the of and and for up to the were The were for of at least and of or for and and or for A proteoglycan was to be present if or more such were identified in at least of the intimal of the of the proteoglycans were the of in of the were as versican and biglycan decorin and lumican and and and In in which more than was used for a the for the were To for the variation in the of intimal from the different arterial all were to the of protein from the intimal analyses were performed using of the proteoglycans were to and at were were with primary to biglycan or lumican to were obtained from to lumican and biglycan were as previously J. J.R. The human lumican and expression in Biol. 1995; Scholar, of of decorin and biglycan in human J. Scholar). were with the at or at were using and which was an were using a To for the variation in the of intimal from the different arterial all were to the of protein from the intimal analyses were performed using internal carotid arteries at the level of the carotid bifurcation and/or internal thoracic arteries at the level of the bifurcation of the intercostal arteries below the second rib were obtained from of these arterial segments are arteries to and are to direct for differences in extracellular matrix analysis revealed of left internal carotid arteries to have atherosclerotic with 16 of the intimal hyperplasia. In contrast, atherosclerosis was present in the internal thoracic arteries from of the atherosclerosis of this It is noteworthy that of the patients atherosclerosis in the internal thoracic 16 eccentric intimal most likely to shear forces at this (8Davies P.F. Flow-mediated endothelial mechanotransduction.Physiol. Rev. 1995; 75: 519-560Google Scholar, 9Garcia-Cardena G. Comander J. Anderson K.R. Blackman B.R. Gimbrone M.A. Biomechanical activation of vascular endothelium as a determinant of its functional phenotype.Proc. Natl. Acad. Sci. U. S. A. 2001; 98: 4478-4485Google Scholar, 10Traub O. Berk B.C. Laminar shear stress: Mechanisms by which endothelial cells transduce an atheroprotective force.Arterioscler. Thromb. Vasc. Biol. 1998; 18: 677-685Google Scholar). the distal ulnar artery J.R. Intimal hyperplasia in the distal ulnar artery: influence of gender and implications for the hypothenar hammer syndrome.Cardiovasc. Pathol. 2004; 13: 20-25Google the internal thoracic artery routinely intimal hyperplasia relatively resistant to the formation of atherosclerosis. The extracellular proteoglycan composition of the intimal hyperplasia from these 16 left internal carotid arteries was compared with that of the intimal hyperplasia from the 16 of internal thoracic The of these are in I. was no these two of with to or there was a of cells in the carotid artery this was not was an enhanced of in the internal carotid arteries compared with the internal thoracic these two of arterial segments were for with both intimal hyperplasia. two of were used to the intimal proteoglycan composition of the preatherosclerotic lesions at these two distinct which markedly in propensity to develop of the arteries used for of intimal cells versus internal thoracic versus internal thoracic artery. in a For arterial the thickened intima was carefully and the proteoglycans were and by with previous studies (20Gutierrez P. O’Brien K.D. Ferguson M. Nikkari S.T. Alpers C.E. Wight T.N. Differences in the distribution of versican, decorin, and biglycan in atherosclerotic human coronary arteries.Cardiovasc. Pathol. 1997; 6: 271-278Google Scholar, 21Kolodgie F.D. Burke A.P. Farb A. Weber D.K. Kutys R. Wight T.N. Virmani R. Differential accumulation of proteoglycans and hyaluronan in culprit lesions: insights into plaque erosion.Arterioscler. Thromb. Vasc. Biol. 2002; 22: 1642-1648Google Scholar, 22Lin H. Kanda T. Hoshino Y. Takase S.-I. Kobayashi I. Nagai R. McManus B.M. Versican, biglycan, and decorin protein expression patterns in coronary arteries: analysis of primary and restenotic lesions.Cardiovasc. Pathol. 1998; 7: 31-37Google Scholar, 23O’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, 25Chung I.-M. Gold H.K. Schwartz S.M. Ikari Y. Reidy M.A. Wight T.N. Enhanced extracellular matrix accumulation in restenosis of coronary arteries after stent deployment.J. Am. Col. Cardiol. 2002; 40: 2072-2081Google Scholar, 26Murdoch A.D. Iozzo R.V. Perlecan: the multidomain heparan sulphate proteoglycan of basement membrane and extracellular matrix.Virchows Archiv. A. Pathol. Anat. 1993; 423: 237-242Google versican, biglycan, and were in the intimal from all of the The of were routinely for these with the that the proteoglycans in intimal hyperplasia. to the class II proteoglycan lumican has been in both atherosclerotic lesions and intimal hyperplasia M. Ishiwata T. Kawahara K. Wang R. Naito Z. Sugisaki Y. Expression of lumican in thickened intima and smooth muscle cells in human coronary atherosclerosis.Exp. Mol. Pathol. 2002; 72: 142-149Google Scholar). with these by lumican was in intimal hyperplasia in most of the In to previous immunohistochemical studies (20Gutierrez P. O’Brien K.D. Ferguson M. Nikkari S.T. Alpers C.E. Wight T.N. Differences in the distribution of versican, decorin, and biglycan in atherosclerotic human coronary arteries.Cardiovasc. Pathol. 1997; 6: 271-278Google decorin was routinely in these preatherosclerotic probably of the enhanced of this In to these previously of human intima, proteoglycans not previously to in human intimal hyperplasia were were the large extracellular proteoglycan and the class II small leucine-rich proteoglycans and prolargin/PRELP (proline arginine-rich end leucine-rich repeat protein). the extracellular proteoglycan composition of human intimal hyperplasia was found to be more complex than previously with up to eight distinct core proteins present in these preatherosclerotic proteoglycans in atherosclerosis-prone and atherosclerosis-resistant of of extracellular proteoglycans membrane proteoglycans I II in a in human vascular the of versican and lumican have been by for an for large in the of these for from the more proteoglycans were Although there was a for versican, biglycan, and in the internal carotid the differences were not This was the for and decorin not However, there was a in the for lumican in the atherosclerosis-prone internal carotid artery compared with from the atherosclerosis-resistant internal thoracic artery. To the enhanced deposition of lumican in the atherosclerosis-prone for proteoglycans was performed these biglycan is present as two distinct with of and two of biglycan have been previously in and vascular cells S. T. D. during of the in Scholar, Wight T.N. Differential expression of small sulfate and by vascular smooth muscle and endothelial cells in Biol. 1991; Scholar). However, the that to these two of biglycan is not of the biglycan present by revealed no the atherosclerosis-prone and atherosclerosis-resistant with the analysis of In addition, there was no in the amounts of the two of biglycan the two arterial not is present as both a with an of and a more with an of The may a core protein and the probably a with R. M. in and lumican in human 1999; Scholar). with the analyses of the there was no in the of present in intima from the two arterial for lumican revealed predominantly from of a proteoglycan of lumican R. M. in and lumican in human 1999; Scholar, J.L. Arterial of a sulfate proteoglycan from Biol. 1991; Scholar, M. J. Expression of lumican in human J. Mol. Biol. 1998; Scholar, H. Ishiwata T. G. of the extracellular matrix lumican expression in smooth muscle cells in Pathol. 2001; Scholar). with the analysis of the there was more lumican present in the intima of the atherosclerosis-prone internal carotid artery than in the atherosclerosis-resistant internal thoracic with the by In vessel the of lumican present in these early lesions with intima/media or the of cells not The of in human intimal hyperplasia is a with important implications for vascular disease. To the of in human intima, for was for was predominantly in the of intimal with immunoreactivity in the intima and The of intimal hyperplasia is to be in proteoglycans H.C. Blankenhorn D.H. Chandler A.B. Glagov S. Insull W. Richardson M. Rosenfeld M.E. Schaffer S.A. Schwartz C.J. Wagner W.D. Wissler R.W. A definition of the intima of human arteries and of its atherosclerosis-prone regions.Circulation. 1992; 85: 391-405Google Scholar). The that in to versican, is a large extracellular proteoglycan to the of the matrix in the of the and transcript have that versican, perlecan, and biglycan are the proteoglycans in human intimal hyperplasia (19Stöcker G. Meyer H.E. Wagener C. Greiling H. Purification and N-terminal amino acid sequence of a chondroitin sulphate/dermatan sulphate proteoglycan isolated from intima/media preparations of human aorta.Biochem. J. 1991; 274: 415-420Google Scholar, P. O’Brien K.D. Ferguson M. Nikkari S.T. Alpers C.E. Wight T.N. Differences in the distribution of versican, decorin, and biglycan in atherosclerotic human coronary arteries.Cardiovasc. Pathol. 1997; 6: 271-278Google Scholar, 21Kolodgie F.D. Burke A.P. Farb A. Weber D.K. Kutys R. Wight T.N. Virmani R. Differential accumulation of proteoglycans and hyaluronan in culprit lesions: insights into plaque erosion.Arterioscler. Thromb. Vasc. Biol. 2002; 22: 1642-1648Google Scholar, 22Lin H. Kanda T. Hoshino Y. Takase S.-I. Kobayashi I. Nagai R. McManus B.M. Versican, biglycan, and decorin protein expression patterns in coronary arteries: analysis of primary and restenotic lesions.Cardiovasc. Pathol. 1998; 7: 31-37Google Scholar, 23O’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, 25Chung I.-M. Gold H.K. Schwartz S.M. Ikari Y. Reidy M.A. Wight T.N. Enhanced extracellular matrix accumulation in restenosis of coronary arteries after stent deployment.J. Am. Col. Cardiol. 2002; 40: 2072-2081Google Scholar, 26Murdoch A.D. Iozzo R.V. Perlecan: the multidomain heparan sulphate proteoglycan of basement membrane and extracellular matrix.Virchows Archiv. A. Pathol. Anat. 1993; 423: 237-242Google Scholar). The analysis reported that versican, biglycan, and are of the intimal extracellular with protein sequence for of these However, this analysis revealed that the proteoglycan core protein composition of human intimal hyperplasia is more complex than previously containing core proteins not previously to in these The roles of of these proteoglycans in the intima to be is of of its large and by which proteoglycans may atherosclerosis is by the direct binding of lipoproteins to the (11Skålén K. Gustafsson M. Rydberg E.K. Hultén L.M. Wiklund O. Innerarity T.L. Borén J. Subendothelial retention of atherogenic lipoproteins in early atherosclerosis.Nature. 2002; 417: 750-754Google Scholar, 12Williams K.J. Arterial wall chondroitin sulfate proteoglycans: diverse molecules with distinct roles in lipoprotein retention and atherogenesis.Curr. Opin. Lipidol. 2001; 12: 477-487Google Scholar, 13Camejo G. Hurt-Camejo E. Wiklund O. Bondjers G. Association of apo B lipoproteins with arterial proteoglycans: pathological significance and molecular basis.Atherosclerosis. 1998; 139: 205-222Google Scholar, 14Williams K.J. Tabas I. The response-to-retention hypothesis of early atherogenesis.Arterioscler. Thromb. Vasc. Biol. 1995; 15: 551-561Google Scholar). Because of the large of aggrecan, and the large of has the to have the for lipoproteins of all of the intimal versican and biglycan have been as important roles in the formation of atherosclerosis T.N. Merrilees M.J. Proteoglycans in atherosclerosis and restenosis, key roles for versican.Circ. Res. 2004; 94: 1158-1167Google Scholar, 23O’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). The of no differences in the of these two proteoglycans atherosclerosis-prone and atherosclerosis-resistant arteries was studies more or in protein in or of which may the two For a there was variation from to in the amounts and the of may have to this no protein was in these The that a in the intimal hyperplasia of atherosclerosis-prone arteries compared with that in atherosclerosis-resistant arteries is the enhanced deposition of lumican in the intima of the atherosclerosis-prone has been to play an important role in and to and this proteoglycan is a of S. A. S. J.L. of lumican in the during Biol. Scholar, W. J. T. lumican from human membrane Sci. Scholar, S. S. inflammatory by Sci. Scholar, S. S. cell and implications in the Res. 2004; Scholar). In addition, lumican has been to to macrophages and to J.L. for a sulfate Sci. 1997; Scholar). prior studies that lumican influence in the vascular intima as as stimulate the formation of the necrotic/lipid core characteristic of atherosclerotic The that formation there is a in the composition of the intimal extracellular matrix of atherosclerosis-prone arteries compared with atherosclerosis-resistant the formation of a necrotic/lipid there to be deposited in the intima of the atherosclerosis-prone an extracellular matrix with the to inflammation and cell The factors the formation of this atherosclerosis-prone matrix are but such factors are likely to play a central role in atherosclerotic the in the of at the of for of with

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