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Thromb Haemost 1998; 79(03): 640-648
DOI: 10.1055/s-0037-1614960
Review Articles
Schattauer GmbH

Phospholipase A2 Modification Enhances Lipoprotein(a) Binding to the Subendothelial Matrix

Jane Hoover-Plow
1   Joseph J. Jacobs Center for Thrombosis and Vascular Biology (FF20), Department of Molecular Cardiology, The Cleveland Clinic Foundation, Cleveland, Ohio
,
Alka Khaitan
1   Joseph J. Jacobs Center for Thrombosis and Vascular Biology (FF20), Department of Molecular Cardiology, The Cleveland Clinic Foundation, Cleveland, Ohio
,
Gunther M. Fless
2   University of Chicago, Department of Medicine, Chicago, Illinois, USA
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Publikationsverlauf

Received 15. Juli 1997

Accepted 29. Oktober 1997

Publikationsdatum:
07. Dezember 2017 (online)

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Summary

Lipoprotein(a), Lp(a), is found in the extracellular matrix in athero-sclerotic plaques, but with a different localization than LDL. A two-compartment system, with a monolayer of endothelial cells forming a barrier, was used to compare the transport, cell binding, and retention of Lp(a) and LDL into the subendothelial matrix. Baseline values for transport and retention of Lp(a) and LDL were not significantly different. Incubation with lipoprotein lipase or sphingomyelinase caused modest and similar increases in transport and retention of the two lipo-proteins. In contrast, incubation with phospholipase A2 (PLA2) resulted in a marked (4-fold) increase in retention of Lp(a) on the subendothelial matrix, but a lesser (2-fold) increase in LDL retention. Moreover, PLA2 treatment of Lp(a) enhanced its binding to individual matrix proteins (fibronectin, laminin, or collagen) by 4-10 times above that of LDL. The enzymatic activity of PLA2 was responsible for its effect on Lp(a) binding. The lysine binding sites of Lp(a) contributed to the increased binding of PLA2-modified Lp(a) to the matrix, and the enhanced lysine binding functions of PLA2-modified Lp(a) was demonstrated by two independent approaches. Thus, PLA2 modification leads to enhanced interactions of lipoproteins with the extracellular matrix, and this effect is more pronounced with Lp(a).

 

  • References

  • 1 Bostom AG, Gagnon DR, Cupples A, Wilson PWF, Jenner JL, Ordovas JM, Schaefer EJ, Castelli WP. A prospective investigation of elevated lipoprotein(a) detected by electrophoresis and cardiovascular disease in women. Circulation 1994; 90: 1688-95.
    CrossrefPubMedGoogle Scholar
  • 2 Terres W, Tatsis E, Pfalzer B, Beil FU, Beisiegel U, Hamm CW. Rapid angiographic progression of coronary artery disease in patients with elevated lipoprotein(a). Circulation 1995; 91: 948-50.
    CrossrefPubMedGoogle Scholar
  • 3 Groves P, Rees A, Bishop A, Morgan R, Ruttley M, Lewis N, Lane I, Hall R. Apolipoprotein(a) concentrations and susceptibility to coronary artery disease in patients with peripheral vascular disease. Br Heart J 1993; 69: 26-30.
    CrossrefPubMedGoogle Scholar
  • 4 Fless GM, Rolih CA, Scanu AM. Heterogeneity of human plasma lipoprotein(a): Isolation and characterization of the lipoprotein subspecies and their apoproteins. J Biol Chem 1984; 259: 11470-8.
    PubMedGoogle Scholar
  • 5 Eaton DL, Fless GM, Kohr WJ, McLean JW, Xu Q-T, Miller CG, Lawn RM, Scanu AM. Partial amino acid sequence of apolipoprotein(a) shows that it is homologous to plasminogen. Proc Natl Acad Sci USA 1987; 84: 3224-8.
    CrossrefPubMedGoogle Scholar
  • 6 Sottrup-Jensen L, Claeys H, Zajdel M, Petersen TE, Magnusson S. The primary structure of human plasminogen: Isolation of two lysine-binding fragments and one “mini”-plasminogen (MW 38,000) by elastase-catalyzed-specific limited proteolysis. In: Progress in Chemical Fibrinolysis and Thrombolysis, Vol. 3. Davidson JF, Rowan RM, Samama MM, Desnoyers PC. (eds). New York: Raven Press; 1978. pp 191-209.
    Google Scholar
  • 7 Miles LA, Dahlberg CM, Plow EF. The cell-binding domains of plasminogen and their function in plasma. J Biol Chem 1988; 263: 11928-34.
    PubMedGoogle Scholar
  • 8 Miles LA, Dahlberg CM, Plescia J, Felez J, Kato K, Plow EF. Role of cell-surface lysines in plasminogen binding to cells: identification of alpha-enolase as a candidate plasminogen receptor. Biochemistry 1991; 30: 1682-91.
    CrossrefPubMedGoogle Scholar
  • 9 Lucas MA, Fretto LJ, McKee PA. The binding of human plasminogen to fibrin and fibrinogen. J Biol Chem 1983; 258: 4249-56.
    PubMedGoogle Scholar
  • 10 Knudsen BS, Silverstein RL, Leung LLK, Harpel PC, Nachman RL. Binding of plasminogen to extracellular matrix. J Biol Chem 1986; 261: 10765-71.
    PubMedGoogle Scholar
  • 11 Wiman B, Lijnen HR, Collen D. On the specific interaction between the lysine-binding sites in plasmin and complementary sites in alpha-2-anti-plasmin and in fibrinogen. Biochim Biophys Acta 1979; 579: 142-54.
    CrossrefPubMedGoogle Scholar
  • 12 Edelberg JM, Gonzalez-Gronow M, Pizzo SV. Lipoprotein(a) inhibits streptokinase-mediated activation of human plasminogen. Biochemistry 1989; 28: 2370-4.
    CrossrefPubMedGoogle Scholar
  • 13 Kluft C, Jie AFH, Los P, deWit E, Havekes L. Functional analogy between lipoprotein(a) and plasminogen in the binding to the kringle 4 binding protein, tetranectin. Biochem Biophys Res Commun 1989; 161: 427-33.
    CrossrefPubMedGoogle Scholar
  • 14 Loscalzo J, Weinfeld M, Fless GM, Scanu AM. Lipoprotein(a), fibrin binding, and plasminogen activation. Arteriosclerosis 1990; 10: 240-5.
    CrossrefPubMedGoogle Scholar
  • 15 Miles LA, Fless GM, Scanu AM, Baynham P, Sebald MT, Skocir P, Curtiss LK, Levin EG, Hoover-Plow JL, Plow EF. Interaction of Lp(a) with plasminogen binding sites on cells. Thromb Haemost 1995; 73: 458-65.
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 16 Cushing GL, Gaubatz JW, Nava ML, Burdick BJ, Bocan TM, Guyton JR, Weilbaecher D, DeBakey ME, Lawrie GM, Morrisett JD. Quantitation and localization of apolipoproteins(a) and B in coronary artery bypass vein grafts resected at reoperation. Arteriosclerosis 1989; 593: 603.
    PubMedGoogle Scholar
  • 17 Pepin JM, O’Neil JA, Hoff HF. Quantification of apo[a] and apoB in human atherosclerotic lesions. J Lipid Res 1991; 32: 317-27.
    PubMedGoogle Scholar
  • 18 Rath M, Niendorf A, Reblin T, Dietel M, Krebber H-J, Beisiegel U. Detection and quantification of lipoprotein(a) in the arterial wall of 107 coronary bypass patients. Arteriosclerosis 1989; 9: 579-92.
    CrossrefPubMedGoogle Scholar
  • 19 Jurgens G, Chen Q, Esterbauer H, Mair S, Ledinski G, Dinges HP. Immunostaining of human autopsy aortas with antibodies to modified apolipoprotein B and apoprotein(a). Arterioscler Thromb 1993; 13: 1689-99.
    CrossrefPubMedGoogle Scholar
  • 20 Jamieson DG, Usher DCl, Rader DJ, Lavi E. Apolipoprotein(a) deposition in atherosclerotic plaques of cerebral vessels: A potential role for endothelial cells in lesion formation. Am J Pathol 1996; 147: 1567-74.
    PubMedGoogle Scholar
  • 21 Salonen E-M, Zitting A, Vaheri A. Laminin interacts with plasminogen and its tissue-type activator. FEBS Lett 1984; 172: 29-32.
    CrossrefPubMedGoogle Scholar
  • 22 Salonen EV, Sakeseki O, Vartio T, Vaheri A, Neilsen LS, Seuthen J. Plasminogen and tissue-type plasminogen activator bind to immobilized fibronectin. J Biol Chem 1985; 260: 12302-7.
    PubMedGoogle Scholar
  • 23 Silverstein RL, Leung LLK, Harpel PC, Nachman RL. Complex formation of platelet thrombospondin with plasminogen. J Clin Invest 1984; 74: 1625-33.
    CrossrefPubMedGoogle Scholar
  • 24 Preissner KT. Specific binding of plasminogen to vitronectin. Evidence for a modulatory role of vitronectin on fibrin(ogen)-induced plasmin formation by tissue plasminogen activator. Biochem Biophys Res Commun 1990; 168: 966-71.
    CrossrefPubMedGoogle Scholar
  • 25 Stack MS, Moser TL, Pizzo SV. Binding of human plasminogen to basement-membrane (type IV) collagen. Biochem J 1992; 284: 103-8.
    CrossrefPubMedGoogle Scholar
  • 26 Andrade-Gordon P, Strickland S. Interaction of heparin with plasminogen activators and plasminogen: Effects on the activation of plasminogen. Biochemistry 1986; 25: 4033-40.
    CrossrefPubMedGoogle Scholar
  • 27 Ericson C, Dahlén GH, Berg K. Interaction of isolated Lp(a) lipoprotein with calcium ions and glycosaminoglycans in vitro. Clin Genet 1977; 11: 433-40.
    PubMedGoogle Scholar
  • 28 Iverius P-H. The interaction between human plasma lipoproteins and connective tissues glycosaminoglycans. J Biol Chem 1972; 247: 2606-13.
    PubMedGoogle Scholar
  • 29 Camejo G, Hurt-Camejo E, Olsson U, Bondjers G. Proteoglycans and lipoproteins in atherosclerosis. Curr Opin Lipidol 1993; 4: 385-91.
    CrossrefPubMedGoogle Scholar
  • 30 Miles LA, Sebald MT, Fless GM, Scanu AM, Hoover-Plow JL, Plow EF. Interaction of lipoprotein(a) [Lp(a)] with the extracellular matrix. Blood 1993; 82: 1785a.
    PubMedGoogle Scholar
  • 31 Pekelharing HLM, Kleinveld HA, Duif PFCCM, Bouma BN, van Rijn HJM. Effect of lipoprotein(a) and LDL on plasminogen binding to extra-cellular matrix and a matrix-dependent plasminogen activation by tissue plasminogen activator. Thromb Haemost 1996; 75: 497-502.
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 32 Hoover-Plow J, Skocir P, Hinman J, Fless G, Scanu A, Plow EF. A quantitative immunoassay for the lysine binding function of lipoprotein(a) in plasma. Fibrinolysis 1994; 8: 349a.
    PubMedGoogle Scholar
  • 33 Chamley-Campbell J, Campbell GR, Ross R. The smooth muscle cell in culture. Physiol Rev 1979; 59: 1-16.
    CrossrefPubMedGoogle Scholar
  • 34 Kudo I, Murakami M, Hara S, Inoue K. Mammalian non-pancreatic phospholipases A2 . Biochim Biophys Acta 1993; 117: 217-31.
    PubMedGoogle Scholar
  • 35 Dennis EA. Diversity of group types, regulation, and function of phospholipase A2 . J Biol Chem 1994; 269: 13057-60.
    PubMedGoogle Scholar
  • 36 Chilton F. Would the real role(s) for secretory PLA2s please stand up. J Clin Invest 1996; 97: 2161-2.
    CrossrefPubMedGoogle Scholar
  • 37 Tew DG, Southan C, Rice SQJ, Lawrence MP, Li H, Boyd HF, Moores K, Gloger IS, Macphee CH. Purification, properites, sequencing, and cloning of a lipoprotein-associated, serine-dependent phospholipase involved in the oxidative modification of low-density lipoproteins. Arterioscler Thromb Vasc Biol 1996; 16: 591-9.
    CrossrefPubMedGoogle Scholar
  • 38 Parthasarathy S, Barnett J. Phospholipase A2 activity of low density lipo-protein: Evidence for an intrinsic phospholipase A2 activity of apoprotein B-100. Proc Natl Acad Sci USA 1990; 87: 9741-5.
    CrossrefPubMedGoogle Scholar
  • 39 Blencowe C, Hermetter A, Kostner GM, Deigner HP. Enhanced association of platelet-activating factor acetylhydrolase with lipoprotein(a) in comparison with low density lipoprotein. J Biol Chem 1995; 270: 31151-7.
    CrossrefPubMedGoogle Scholar
  • 40 Hoover-Plow JL, Miles LA, Fless GM, Scanu AM, Plow EF. Comparison of the lysine binding functions of lipoprotein(a) and plasminogen. Biochemistry 1993; 32: 13681-7.
    CrossrefPubMedGoogle Scholar
  • 41 Snyder ML, Polacek D, Scanu AM, Fless GM. Comparative binding and degradation of lipoprotein(a) and low density lipoprotein by human monocyte derived macrophages. J Biol Chem 1992; 267: 339-46.
    PubMedGoogle Scholar
  • 42 Deutsch DG, Mertz ET. Plasminogen: purification from human plasma by affinity chromatography. Science 1970; 170: 1095-6.
    CrossrefPubMedGoogle Scholar
  • 43 Furbee Jr. JW, Fless GM. Evaluation of common electrophoretic methods in determining the molecular weight of apolipoprotein(a) polymorphs. Anal Biochem. 1996 234. In press.
    PubMedGoogle Scholar
  • 44 Markwell MAK, Haas SM, Bieber LL, Tolbert NE. A modification of the Lowry procedure to simplify protein determination in membrane and lipo-protein samples. Anal Biochem 1978; 87: 206-10.
    CrossrefPubMedGoogle Scholar
  • 45 Shepherd J, Bedford DK, Morgan HG. Radioiodination of human low density lipoprotein: a comparison of four methods. Clin Chim Acta 1976; 66: 97-109.
    CrossrefPubMedGoogle Scholar
  • 46 Miles LA, Plow EF. Binding and activation of plasminogen on the platelet surface. J Biol Chem 1985; 260: 4303-11.
    PubMedGoogle Scholar
  • 47 Edgell C-JS, McDonald CC, Graham JB. Permanent cell line expressing human factor VIII-related antigen established by hybridization. Proc Natl Acad Sci USA 1983; 80: 3734-7.
    CrossrefPubMedGoogle Scholar
  • 48 Nakano T, Ohara O, Teraoka H, Arita H. Group II phospholipase A2 mRNA synthesis is stimulated by two distinct mechanisms in rat vascular smooth muscle cells. FEBS Lett 1990; 261: 171-4.
    CrossrefPubMedGoogle Scholar
  • 49 Aznar-Salatti J, Bastida E, Haas TA, Escolar G, Ordinas A, de Groot PHG, Buchanan MR. Platelet adhesion to exposed endothelial cell extracellular matrixes is influenced by the method of preparation. Arterioscler Thromb 1991; 11: 436-42.
    CrossrefPubMedGoogle Scholar
  • 50 Gurakar-Osborne A, Prete PE. Rapid assay of phospholipase A2 activity in plasma and synovial fluid. Clin Chem 1995; 41: 118-9.
    PubMedGoogle Scholar
  • 51 Suits AG, Chait A, Aviram M, Heinecke JW. Phagocytosis of aggregated lipoprotein by macrophages: Low density lipoprotein receptor-dependent foam-cell formation. Proc Natl Acad Sci USA 1989; 86: 2713-7.
    CrossrefPubMedGoogle Scholar
  • 52 Hoover-Plow JL, Boonmark N, Skocir P, Lawn R, Plow EF. A quantitative immunoassay for the lysine-binding function of lipoprotein(a): Application to recombinant apo(a) and lipoprotein(a) in plasma, and modified lipoprotein(a). Arterioscler Thromb Vasc Biol 1996; 16: 656-64.
    CrossrefPubMedGoogle Scholar
  • 53 Parikh I, March S, Cuatrecasas P. Topics in the methodology of substitution reactions with agarose. Methods Enzymol 1974; 34: 77-80.
    PubMedGoogle Scholar
  • 54 Alexander JJ, Miguel R, Piotrowski JJ. Calcium regulation of endothelial permeability to low-density lipoprotein. J Surg Res 1995; 59 (03) 371-7.
    CrossrefPubMedGoogle Scholar
  • 55 Saxena U, Klein MG, Vanni TM, Goldberg IJ. Lipoprotein lipase increases low density lipoprotein retention by subendothelial cell matrix. J Clin Invest 1992; 89: 373-80.
    CrossrefPubMedGoogle Scholar
  • 56 Hennig B, Toborek M, Boissonneault GA, Shantha NC, Decker EA, Oeltgen PR. Animal and plant fats selectively modulate oxidizability of rabbit LDL and LDL-mediated disruption of endothelial barrier function. J Nutr 1995; 125: 2045-54.
    CrossrefPubMedGoogle Scholar
  • 57 Rabiet M-J, Plantier J-L, Rival Y, Genoux Y, Lampugnani M-G, Dejana E. Thrombin-induced increase in endothelial permeability is associated with changes in cell-to-cell junction organization. Arterioscler Thromb Vasc Biol 1996; 16: 488-96.
    CrossrefPubMedGoogle Scholar
  • 58 King GL, Johnson SM. Receptor-mediated transport of insulin across endothelial cells. Science 1985; 227: 1583-6.
    CrossrefPubMedGoogle Scholar
  • 59 Shasby DM, Lind SE, Shasby SS, Goldsmith JC, Hunninghake GW. Reversible oxidant-induced increases in albumin transfer across cultured endothelium: alterations in cell shape and calcium homeostasis. Blood 1985; 3: 605-14.
    PubMedGoogle Scholar
  • 60 Shasby DM, Shasby SS. Active transendothelial transport of albumin: Interstitium to lumen. Circ Res 1985; 57: 903-8.
    CrossrefPubMedGoogle Scholar
  • 61 Tabas I, Li Y, Brocia RW, Xu SW, Swenson TL, Williams KJ. Lipoprotein lipase and sphingomyelinase synergistically enhance the association of atherogenic lipoproteins with smooth muscle cells and extracellular matrix. J Biol Chem 1993; 268: 20419-32.
    PubMedGoogle Scholar
  • 62 Eisenberg S, Sehayek E, Olivecrona T, Vlodavsky I. Lipoprotein lipase enhances binding of lipoproteins to heparan sulfate on cell surfaces and extracellular matrix. J Clin Invest 1992; 90: 2013-21.
    CrossrefPubMedGoogle Scholar
  • 63 Marinetti GV. Chromatographic separation, identification, and analysis of phosphatides. J Lipid Res 1962; 3: 1-20.
    PubMedGoogle Scholar
  • 64 Kreuzer J, Lloyd MB, Bok D, Fless GM, Scanu AM, Lusis AJ, Haberland ME. Lipoprotein(a) displays increased accumulation compared with low-density lipoprotein in the murine arterial wall. Chem Phys Lipids 1994; 67/68: 175-90.
    CrossrefPubMedGoogle Scholar
  • 65 Nielsen LB, Nordestgaard G, Stender S, Niendorf A, Kjeldsen K. Transfer of lipoprotein(a) and LDL into aortic intima in normal and in cholesterolfed rabbits. Arterioscler Thromb Vasc Biol 1995; 15: 1492-502.
    CrossrefPubMedGoogle Scholar
  • 66 Natarajan MK, Fong BS, Angel A. Enhanced binding of phospholipase-A2-modified low density lipoprotein by human adipocytes. Biochem Cell Biol 1990; 68: 1243-9.
    CrossrefPubMedGoogle Scholar
  • 67 Aviram M, Maor I. Phospholipase A2-modified LDL is taken up at enhanced rate by macrophages. Biochem Biophys Res Commun 1992; 185: 465-72.
    CrossrefPubMedGoogle Scholar
  • 68 Kleinman Y, Krul ES, Burnes M, Aronson W, Pfleger B, Schonfeld G. Lipolysis of LDL with phospholipase A2 alters the expression of selected apoB-100 epitopes and the interaction of LDL with cells. J Lipid Res 1988; 29: 729-43.
    PubMedGoogle Scholar
  • 69 Labeque R, Mullon CJP, Ferreira JPM, Lees RS, Langer R. Enzymatic modification of plasma low density lipoproteins in rabbits: A potential treatment for hypercholesterolemia. Proc Natl Acad Sci USA 1993; 90: 3476-80.
    CrossrefPubMedGoogle Scholar
  • 70 Aggerbeck LP, Kezdy FJ, Scanu AM. Enzymatic probes of lipoprotein structure: Hydrolysis of human serum low density lipoprotein-2 by phospholipase A2 . J Biol Chem 1976; 251: 3823-30.
    PubMedGoogle Scholar
  • 71 Gorshkova IN, Menschikowski M, Jaross W. Alterations in the physio-chemical characteristics of low and high density lipoproteins after lipolysis with phospholipase A2 . Biochim Biophys Acta 1996; 300: 103-13.
    PubMedGoogle Scholar
  • 72 Hermetter A, Sommer A, Gorges R, Prenner E, Kostner GM, Paltauf F. Apoprotein-phospholipid interactions in Lp(a). Chem Phys Lipids 1994; 67/68: 115-9.
    CrossrefPubMedGoogle Scholar
  • 73 Fless GM, Furbee Jr. J, Snyder ML, Meredith SC. Ligand-induced conformational change of lipoprotein(a). Biochemistry 1996; 35: 2289-98.
    CrossrefPubMedGoogle Scholar
  • 74 Huby T, Doucet C, Dieplinger H, Chapman J, Thillet J. Structural domains of apolipoprotein(a) and its interaction with apolipoprotein B-100 in the lipoprotein(a) particle. Biochemistry 1994; 33: 3335-41.
    CrossrefPubMedGoogle Scholar
  • 75 Prassl R, Schuster B, Abuja PM, Zechner M, Kostner GM, Laggner P. A comparison of structure and thermal behavior in human plasma lipoprotein(a) and low-density lipoprotein. Calorimetry and small-angle X-ray scattering. Biochemistry 1995; 34: 3795-801.
    CrossrefPubMedGoogle Scholar
  • 76 Sommer A, Prenner E, Gorges R, Stutz H, Grillhofer H, Kostner GM, Paltauf F, Hermetter A. Organization of phosphatidylcholine and sphingomyelin in the surface monolayer of low density lipoprotein and lipoprotein(a) as determined by time-resolved fluorometry. J Biol Chem 1992; 267: 24217-22.
    PubMedGoogle Scholar
  • 77 Koschinsky ML, Côté GP, Gabel B, Van der Hoek YY. Identification of the cysteine residue in apolipoprotein(a) that mediates extracellular coupling with apolipoprotein B-100. J Biol Chem 1993; 268: 19819-25.
    PubMedGoogle Scholar
  • 78 Scanu AM, Miles LA, Pfaffinger D, Fless GM, Jackson E, Hoover-Plow JL, Brunck T, Plow EF. Rhesus monkey Lp(a) binds to lysine-Sepharose and U937 monocytoid cells less efficiently than human Lp(a). Evidence for a dominant role of kringle 437. J Clin Invest 1993; 91: 283-91.
    CrossrefPubMedGoogle Scholar
  • 79 LoGrasso PV, Cornell-Kennon S, Boettcher BR. Cloning, expression, and characterization of human apolipoprotein(a) Kringle IV37. J Biol Chem 1994; 269: 21820-7.
    PubMedGoogle Scholar
  • 80 Ernst A, Helmhold M, Brunner C, Pethö-Schramm A, Armstrong VW, Müller H-J. Identification of two functionally distinct lysine-binding sites in kringle 37 and in kringles 32-36 of human apolipoprotein(a). J Biol Chem 1995; 270: 6227-34.
    CrossrefPubMedGoogle Scholar
  • 81 Edelstein C, Mandala M, Pfaffinger D, Scanu AM. Determinants of lipoprotein(a) assembly: A study of wild-type and mutant apolipoprotein(a) phenotypes isolated from human and rhesus monkey lipoprotein(a) under mild reductive conditions. Biochemistry 1995; 34: 16483-92.
    CrossrefPubMedGoogle Scholar
  • 82 Gabel BR, May LF, Marcovina SM, Koschinsky ML. Lipoprotein(a) assembly: Quantitative assessment of the role of apo(a) kringle IV types 2-10 in particle formation. Arterioscler Thromb Vasc Biol 1996; 16: 1559-67.
    CrossrefPubMedGoogle Scholar
  • 83 Trieu VN, McConathy WJ. A Two-step Model for Lipoprotein(a) Formation. J Biol Chem 1995; 270: 15471-4.
    CrossrefPubMedGoogle Scholar