Skip to main content
SpringerLink
Log in

Lipoprotein(a) as an Emerging Risk Factor for Atherothrombosis

Principles from Bench to Bedside

  • Chapter
Therapeutic Lipidology

Part of the book series: Contemporary Cardiology ((CONCARD))

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 259.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 329.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Superko HR, Hecht HS. Metabolic disorders contribute to subclinical coronary atherosclerosis in patients with coronary calcification. Am J Cardiol 2001;88:260–4.

    Article  PubMed  CAS  Google Scholar 

  2. Albers JJ, Kennedy H, Marcovina SM. Evidence that Lp(a) contains one molecule of apo(a) and one molecule of apo B: evaluation of amino acid analysis data. J Lipid Res 1996;37:192–6.

    PubMed  CAS  Google Scholar 

  3. Koschinsky ML, Côté GP, Gabel BR, 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.

    PubMed  CAS  Google Scholar 

  4. Callow MJ, Rubin EM. Site-specific mutagenesis demonstrates that cysteine 4326 of apolipoprotein B is required for covalent linkage with apolipoprotein(a) in vivo. J Biol Chem 1995;270:23914–7.

    Article  PubMed  CAS  Google Scholar 

  5. Trieu VN, McConathy WJ. A two-step model for lipoprotein(a) formation. J Biol Chem 1995;270:15471–4.

    Article  PubMed  CAS  Google Scholar 

  6. Becker L, Cook PM, Wright TG, Koschinsky ML. Quantitative evaluation of the contribution of weak lysine-binding sites present within apolipoprotein(a) kringle IV types 6–8 to lipoprotein(a) assembly. J Biol Chem 2004;279:2679–88.

    Article  PubMed  CAS  Google Scholar 

  7. Becker L, McLeod RS, Marcovina SM, Yao Z, Koschinsky ML. Identification of a critical lysine residue in apolipoprotein B-100 that mediates noncovalent interaction with apolipoprotein(a). J Biol Chem 2001;276:36155–62.

    Article  PubMed  CAS  Google Scholar 

  8. Becker L, Webb BA, Chitayat S, Nesheim ME, Koschinsky ML. A ligand-induced conformational change in apolipoprotein(a) enhances covalent Lp(a) formation. J Biol Chem 2003;278:14074–81.

    Article  PubMed  CAS  Google Scholar 

  9. Xu S. Apolipoprotein(a) binds to low density lipoprotein at two distant sites in lipoprotein(a). Biochemistry 1998;37:9284–94.

    Article  PubMed  CAS  Google Scholar 

  10. White AL, Rainwater DL, Lanford RE. Intracellular maturation of apolipoprotein(a) and assembly of lipoprotein(a) in primary baboon hepatocytes. J Lipid Res 1993;34:509–17.

    PubMed  CAS  Google Scholar 

  11. Frank S, Krasznai K, Durovic S, Lobentanz EM, Dieplinger H, Wagner E, Zatloukal K, Cotten M, Utermann G, Kostner GM, et al. High-level expression of various apolipoprotein(a) isoforms by “transferrinfection”: the role of kringle IV sequences in the extracellular association with low-density lipoprotein. Biochemistry 1994;33:12329–39.

    Article  PubMed  CAS  Google Scholar 

  12. White, AL, Lanford, RE. Cell surface assembly of lipoprotein(a) in primary cultures of baboon hepatocytes. J Biol Chem 1994;269:28716–23.

    PubMed  CAS  Google Scholar 

  13. Fless GM, ZumMallen ME, Scanu AM. Physicochemical properties of apolipoprotein(a) and lipoprotein(a–) derived from the dissociation of human plasma lipoprotein(a). J Biol Chem 1986;261:8712–8.

    PubMed  CAS  Google Scholar 

  14. Kraft HG, Menzel HJ, Hoppichler F, Vogel W, Utermann G. Changes of genetic apolipoprotein phenotypes caused by liver transplantation. Implications for apolipoprotein synthesis. J Clin Invest 1989;83:137–40.

    PubMed  CAS  Google Scholar 

  15. McLean JW, Tomlinson JE, Kuang W-J, Eaton DL, Chen EY, Fless GM, Scanu AM, Lawn RM. cDNA sequence of human apolipoprotein(a) is homologous to plasminogen. Nature 1987;330:132–7.

    Article  PubMed  CAS  Google Scholar 

  16. Gabel BR, Koschinsky ML. Analysis of the proteolytic activity of a recombinant form of apolipoprotein(a). Biochemistry 1995;34:15777–84.

    Article  PubMed  CAS  Google Scholar 

  17. van der Hoek YY, Wittekoek ME, Beisiegel U, Kastelein JJ, Koschinsky ML. The apolipoprotein(a) kringle IV repeats which differ from the major repeat kringle are present in variably sized isoforms. Hum Mol Genet 1993;2:361–6.

    Article  PubMed  Google Scholar 

  18. Lackner C, Cohen JC, Hobbs HH. Molecular definition of the extreme size polymorphism in apolipoprotein(a). Hum Mol Genet 1993;2:933–40.

    Article  PubMed  CAS  Google Scholar 

  19. Sangrar W, Marcovina SM, Koschinsky, ML. Expression and characterization of apolipoprotein(a) kringle IV types 1, 2 and 10 in mammalian cells. Protein Eng 1993;7:723–31.

    Google Scholar 

  20. 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.

    PubMed  CAS  Google Scholar 

  21. Ernst A, Helmhold M, Brunner C, Petho-Schramm A, Armstrong VW, Muller HJ. Identification of two functionally distinct lysine binding sites in kringle 37 and in kringles 32–36 of human apolipoprotein(a). J Biol Chem 1994;270:6227–34.

    Google Scholar 

  22. Rahman MN, Becker L, Petrounevitch V, Hill BC, Jia Z, Koschinsky ML. Comparative analyses of the lysine binding site properties of apolipoprotein(a) kringle IV types 7 and 10. Biochemistry 2002;41:1149–55.

    Article  PubMed  CAS  Google Scholar 

  23. Kochl S, Fresser F, Lobentanz E, Baier G, Utermann G. Novel interaction of apolipoprotein(a) with beta-2 glycoprotein I mediated by the kringle IV domain. Blood 1997;90:1482–9.

    PubMed  CAS  Google Scholar 

  24. Kapetanopoulos A, Fresser F, Millonig G, Shaul Y, Baier G, Utermann G. Direct interaction of the extracellular matrix protein DANCE with apolipoprotein(a) mediated by the kringle IV-type 2 domain. Mol Genet Genomics 2002;267:440–6.

    Article  PubMed  CAS  Google Scholar 

  25. Boerwinkle E, Leffert CC, Lin J, Lackner C, Chiesa G, Hobbs HH. Apolipoprotein(a) gene accounts for greater than 90% of the variation in plasma lipoprotein(a) concentrations. J Clin Invest 1990;90:52–60.

    Google Scholar 

  26. Utermann G, Menzel HJ, Kraft HG, Duba HC, Kemmler HG, Seitz C. Lp(a) glycoprotein phenotypes. Inheritance and relation to Lp(a)-lipoprotein concentrations in plasma. J Clin Invest 1987;80:458–65.

    PubMed  CAS  Google Scholar 

  27. Brunner C, Lobentanz EM, Petho-Schramm A, Ernst A, Kang C, Dieplinger H, Muller HJ, Utermann G. The number of identical kringle IV repeats in apolipoprotein(a) affects its processing and secretion by HepG2 cells. J Biol Chem 1996;271:32403–10.

    Article  PubMed  CAS  Google Scholar 

  28. Marcovina SM, Albers JJ, Wijsman E, Zhang Z, Chapman NH, Kennedy H. Differences in Lp(a) concentrations and apo(a) polymorphs between Black and White Americans. J Lipid Res 1996;37:2569–85.

    PubMed  CAS  Google Scholar 

  29. Rubin J, Paultre F, Tuck CH, Holleran S, Reed RG, Pearson TA, Thomas CM, Ramakrishnan R, Berglund L. Apolipoprotein(a) genotype influences isoform dominance pattern differently in African Americans and Caucasians. J Lipid Res 2002;43:234–44.

    PubMed  CAS  Google Scholar 

  30. Bergund L, Ramakrishnan R. Lipoprotein(a). An elusive cardiovascular risk factor. Arterioscler Thromb Vasc Biol 2004;24:2219–26.

    Article  CAS  Google Scholar 

  31. Paultre F, Pearson TA, Weil HF, Tuck CH, Myerson M, Rubin J, Francis CK, Marx HF, Philbin EF, Reed RG, et al. High levels of Lp(a) with a small apo(a) isoform are associated with coronary artery disease in African American and White men. Arterioscler Thromb Vasc Biol 2000;20:2619–24.

    PubMed  CAS  Google Scholar 

  32. Marcovina SM, Koschinsky ML. Lipoprotein(a): structure, measurement and clinical significance. In: Rifai N, Warnick GR, Dominiczak MH, eds. Handbook of Lipoprotein Testing. 2nd ed. Washington, DC: AACC Press, 2000:345–85.

    Google Scholar 

  33. Armstrong VW, Schleef J, Thiery J, Muche R, Schuff-Werner P, Eisenhauer T, Seidel D. Effect of HELP-LDL-apheresis on serum concentrations of human lipoprotein(a): kinetic analysis of the post-treatment return to baseline levels. Eur J Clin Invest 1989;19:235–40.

    PubMed  CAS  Google Scholar 

  34. Pokrovsky SN, Adamova I, Afanasieva OY, Benevolenskaya GF. Immunosorbent for selective removal of lipoprotein(a) from human plasma: in vitro study. Artif Organs 1991;15:136–40.

    Article  PubMed  CAS  Google Scholar 

  35. Crouse JR, III. New developments in the use of niacin for treatment of hyperlipidemia: new considerations in the use of an old drug. Coron Artery Dis 1996;7:321–6.

    Article  PubMed  Google Scholar 

  36. Sirtori CR, Calabresi L, Ferrara S, Pazzucconi F, Bondioli A, Baldassarre D, Birreci A, Koverech A. L-carnitine reduces plasma lipoprotein(a) levels in patients with hyper Lp(a). Nutr Metab Cardiovasc Dis 2000;10:247–51.

    PubMed  CAS  Google Scholar 

  37. Dalessandri KM. Reduction of lipoprotein(a) in postmenopausal women. Arch Intern Med 2001;161:772–3.

    Article  PubMed  CAS  Google Scholar 

  38. Crook D, Sidhu M, Seed M, O’Donnell M, Stevenson JC. Lipoprotein Lp(a) levels are reduced by danazol, an anabolic steroid. Atherosclerosis 1992;92:41–7.

    Article  PubMed  CAS  Google Scholar 

  39. Haenggi W, Riesen W, Birkhaeuser MH. Postmenopausal hormone replacement therapy with Tibolone decreases serum lipoprotein(a). Eur J Clin Chem Clin Biochem 199;31:645–50.

    Google Scholar 

  40. Rymer J, Crook D, Sidhu M, Chapman M, Stevenson JC. Effects of tibolone on serum concentrations of lipoprotein(a) in postmenopausal women. Acta Endocrinol (Copenh) 1993;128:259–62.

    CAS  Google Scholar 

  41. Henriksson P, Angelin B, Berglund L. Hormonal regulation of serum Lp(a) levels. Opposite effects after estrogen treatment and orchidectomy in males with prostatic carcinoma. J Clin Invest 1992;89:1166–71.

    PubMed  CAS  Google Scholar 

  42. Shewmon DA, Stock JL, Rosen CJ, Heiniluoma KM, Hogue MM, Morrison A, Doyle EM, Ukena T, Weale V, Baker S. Tamoxifen and estrogen lower circulating lipoprotein(a) concentrations in healthy postmenopausal women. Arterioscler Thromb 1994;14:1586–93.

    PubMed  CAS  Google Scholar 

  43. Plenge JK, Hernandez TL, Weil KM, Poirier P, Grunwald GK, Marcovina SM, Eckel RH. Simvastatin lowers C-reactive protein within 14 days: an effect independent of low-density lipoprotein cholesterol reduction. Circulation 2002;106:1447–52.

    Article  PubMed  CAS  Google Scholar 

  44. Dujovne CA, Harris WS, Altman R, Overhiser RW, Black DM. Effect of atorvastatin on hemorheologic-hemostatic parameters and serum fibrinogen levels in hyperlipidemic patients. Am J Cardiol 2000;85:350–3.

    Article  PubMed  CAS  Google Scholar 

  45. Cobbaert C, Jukema JW, Zwinderman AH, Withagen AJ, Lindemans J, Bruschke AV. Modulation of lipoprotein(a) atherogenicity by high density lipoprotein cholesterol levels in middle-aged men with symptomatic coronary artery disease and normal to moderately elevated serum cholesterol. Regression Growth Evaluation Statin Study (REGRESS) Study Group. J Am Coll Cardiol 1997;30:1491–9.

    Article  PubMed  CAS  Google Scholar 

  46. Duriez P, Dallongeville J, Fruchart JC. Lipoprotein(a) as a marker for coronary heart disease. Br J Clin Pract Suppl 1996;77A:54–61.

    PubMed  CAS  Google Scholar 

  47. Gonbert S, Malinsky S, Sposito AC, Laouenan H, Doucet C, Chapman MJ, Thillet J. Atorvastatin lowers lipoprotein(a) but not apolipoprotein(a) fragment levels in hypercholesterolemic subjects at high cardiovascular risk. Atherosclerosis 2002;164:305–11.

    Article  PubMed  CAS  Google Scholar 

  48. Akaike M, Azuma H, Kagawa A, Matsumoto K, Hayashi I, Tamura K, Nishiuchi T, Iuchi T, Takamori N, Aihara K, et al. Effect of aspirin treatment on serum concentrations of lipoprotein(a) in patients with atherosclerotic diseases. Clin Chem 2002;48:1454–9.

    PubMed  CAS  Google Scholar 

  49. Kiortsis DN, Tzotzas T, Giral P, Bruckert E, Beucler I, Valsamides S, Turpin G. Changes in lipoprotein(a) levels and hormonal correlations during a weight reduction program. Nutr Metab Cardiovasc Dis 2001;11:153–7.

    PubMed  CAS  Google Scholar 

  50. Jenkins DJ, Kendall CW, Marchie A, Parker TL, Connelly PW, Qian W, Haight JS, Faulkner D, Vidgen E, Lapsley KG, et al. Dose response of almonds on coronary heart disease risk factors: blood lipids, oxidized low-density lipoproteins, lipoprotein(a), homocysteine, and pulmonary nitric oxide: a randomized, controlled, crossover trial. Circulation 2002;106:1327–32.

    Article  PubMed  CAS  Google Scholar 

  51. Ginsberg HN, Kris-Etherton P, Dennis B, Elmer PJ, Ershow A, Lefevre M, Pearson T, Roheim P, Ramakrishnan R, Reed R, et al. Effects of reducing dietary saturated fatty acids on plasma lipids and lipoproteins in healthy subjects: the DELTA Study, protocol 1. Arterioscler Thromb Vasc Biol 1998;18:441–9.

    PubMed  CAS  Google Scholar 

  52. Executive Summary of the Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). J Am Med Assoc 2001;285:2486–97.

    Google Scholar 

  53. Cheng SW, Ting AC, Wong J. Lipoprotein(a) and its relationship to risk factors and severity of atherosclerotic peripheral vascular disease. Eur J Vasc Endovasc Surg 1997;14:17–23.

    Article  PubMed  CAS  Google Scholar 

  54. Peng DQ, Zhao SP, Wang JL. Lipoprotein(a) and apolipoprotein E epsilon 4 as independent risk factors for ischemic stroke. J Cardiovasc Risk 1999;6:1–6.

    PubMed  CAS  Google Scholar 

  55. Marcovina SM, Hegele RA, Koschinsky ML. Lipoprotein(a) and coronary heart disease risk. Curr Cardiol Rep 1999;1:105–11.

    Article  PubMed  CAS  Google Scholar 

  56. Marcovina SM, Koschinsky ML. Lipoprotein(a) as a risk factor for coronary artery disease. Am J Cardiol 1998;82:57U-66U

    Article  PubMed  CAS  Google Scholar 

  57. Marcovina SM, Koschinsky ML, Albers JJ, Skarlatos S. Report of the National Heart, Lung, and Blood Institute Workshop on Lipoprotein(a) and Cardiovascular Disease: recent advances and future directions. Clin Chem 2003;49:1785–96.

    Article  PubMed  CAS  Google Scholar 

  58. Craig WY, Neveux LM, Palomaki GE, Cleveland MM, Haddow JE. Lipoprotein(a) as a risk factor for ischemic heart disease: meta-analysis of prospective studies. Clin Chem 1998;44:2301–6.

    PubMed  CAS  Google Scholar 

  59. Danesh J, Collins R, Peto R. Lipoprotein(a) and coronary heart disease. Meta-analysis of prospective studies. Circulation 2000;102:1082–5.

    PubMed  CAS  Google Scholar 

  60. Sharrett AR, Ballantyne CM, Coady SA, Heiss G, Sorlie PD, Catellier D, Patsch W, Atherosclerosis Risk in Communities Study Group. Coronary heart disease prediction from lipoprotein cholesterol levels, triglycerides, lipoprotein(a), apolipoproteins A-I and B, and HDL density subfractions: The Atherosclerosis Risk in Communities (ARIC) Study. Circulation 2001;104:1108–13.

    Article  PubMed  CAS  Google Scholar 

  61. Glader CA, Birgander LS, Stenlund H, Dahlen GH. Is lipoprotein(a) a predictor for survival in patients with established coronary artery disease? Results from a prospective patient cohort study in northern Sweden. J Intern Med 2002;252:27–35.

    Article  PubMed  Google Scholar 

  62. Maher VM, Brown BG, Marcovina SM, Hillger LA, Zhao XQ, Albers JJ. Effects of lowering elevated LDL cholesterol on the cardiovascular risk of lipoprotein(a). J Am Med Assoc 1995;274:1771–4.

    Article  CAS  Google Scholar 

  63. Luc G, Bard JM, Arveiler D, Ferrieres J, Evans A, Amouyel P, Fruchart JC, Ducimetiere P, PRIME Study Group. Lipoprotein (a) as a predictor of coronary heart disease: the PRIME Study. Atherosclerosis 2002;163:377–84.

    Article  PubMed  CAS  Google Scholar 

  64. Cantin B, Gagnon F, Moorjani S, Despres JP, Lamarche B, Lupien PJ, Dagenais GR. Is lipoprotein(a) an independent risk factor for ischemic heart disease in men? The Quebec Cardiovascular Study. J Am Coll Cardiol 1998;31:519–25.

    Article  PubMed  CAS  Google Scholar 

  65. von Eckardstein A, Schulte H, Cullen P, Assmann G. Lipoprotein(a) further increases the risk of coronary events in men with high global cardiovascular risk. J Am Coll Cardiol 2001;37:434–9.

    Article  Google Scholar 

  66. Marcovina SM, Koschinsky ML. Evaluation of lipoprotein(a) as a prothrombotic factor: progress from bench to bedside. Curr Opin Lipidol 2003;14:361–6.

    Article  PubMed  CAS  Google Scholar 

  67. Marcucci R, Liotta AA, Cellai AP, Rogolino A, Gori AM, Giusti B, Poli D, Fedi S, Abbate R, Prisco D. Increased plasma levels of lipoprotein(a) and the risk of idiopathic and recurrent venous thromboembolism. Am J Med 2003;115:667–8.

    Article  CAS  Google Scholar 

  68. Nowak-Gottl U, Strater R, Heinecke A, Junker R, Koch HG, Schuierer G, von Eckardstein A. Lipoprotein(a) and genetic polymorphisms of clotting Factor V, prothrombin, and methylenetetrahydrofolate reductase are risk factors of spontaneous ischemic stroke in childhood. Blood 1999;94:3678–82.

    PubMed  CAS  Google Scholar 

  69. Strater R, Becker S, von Eckardstein A, Heinecke A, Gutsche S, Junker R, Kurnik K, Schobess R, Nowak-Gottl U. Prospective assessment of risk factors for recurrent stroke during childhood. Lancet 2002;360:1540–5.

    Article  PubMed  Google Scholar 

  70. Dahl T, Kontny F, Slagsvold CE, Christophersen B, Abildgaard U, Odegaard OR, Morkrid L, Dale J. Lipoprotein(a), other lipoproteins and hemostatic profiles in patients with ischemic stroke: the relation to cardiogenic embolism. Cerebrovasc Dis 2000;10:110–7.

    Article  PubMed  CAS  Google Scholar 

  71. Kronenberg F, Kronenberg MF, Kiechl S, Trenkwalder E, Santer P, Oberhollenzer F, Egger G, Utermann G, Willeit J. Role of lipoprotein(a) and apolipoprotein(a) phenotype in atherogenesis: prospective results from the Bruneck study. Circulation 1999;100:1154–60.

    PubMed  CAS  Google Scholar 

  72. Wild SH, Fortmann SP, Marcovina SM. A prospective case-control study of lipoprotein(a) levels and apo(a) size and risk of coronary heart disease in Stanford Five-City Project participants. Arterioscler Thromb Vasc Biol 1997;17:239–45.

    PubMed  CAS  Google Scholar 

  73. Paultre F, Tuck CH, Boden-Albala B, Kargman DE, Todd E, Jones J, Paik MC, Sacco RL, Berglund L. Relation of Apo(a) size to carotid atherosclerosis in an elderly multiethnic population. Arterioscler Thromb Vasc Biol 2002;22:141–6.

    Article  PubMed  CAS  Google Scholar 

  74. Shai I, Rimm EB, Hankinson SE, Cannuscio C, Curhan G, Manson JE, Rifai N, Stampfer MJ, Ma J. Lipoprotein(a) and coronary heart disease among women: beyond a cholesterol carrier? Eur Heart J 2005;26:1633–9.

    Article  PubMed  CAS  Google Scholar 

  75. Orth-Gomer K, Mittleman MA, Schenck-Gustafsson K, Wamala SP, Eriksson M, Belkic K, Kirkeeide R, Svane B, Ryden L. Lipoprotein(a) as a determinant of coronary heart disease in young women. Circulation 1997;95:329–34.

    PubMed  CAS  Google Scholar 

  76. Ariyo AA, Thach C, Tracy R. Lp(a) lipoprotein, vascular disease, and mortality in the elderly. N Engl J Med 2003;349:2108–15.

    Article  PubMed  CAS  Google Scholar 

  77. Ridker M, Hennekens CH, Buring JE, Rifai N. C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med 2000;342:836–43.

    Article  PubMed  CAS  Google Scholar 

  78. Wu HD, Berglund L, Dimayuga C, Jones J, Sciacca RR, Di Tullio MR, Homma S. High lipoprotein(a) levels and small apolipoprotein(a) sizes are associated with endothelial dysfunction in a multiethnic cohort. J Am Coll Cardiol 2004;43:1828–33.

    Article  PubMed  CAS  Google Scholar 

  79. Emanuele E, Peros E, Minoretti P, D’Angelo A, Montagna L, Falcone C, Geroldi D. Significance of apolipoprotein(a) phenotypes in acute coronary syndromes: relation with clinical presentation. Clin Chim Acta 2004;350:159–65.

    Article  PubMed  CAS  Google Scholar 

  80. Rifai N, Ma J, Sacks FM, Ridker PM, Hernandez WJ, Stampfer MJ, Marcovina SM. Apolipoprotein(a) size and lipoprotein(a) concentrations and future risk of angina pectoris with evidence of severe coronary atherosclerosis in men: The Physician’s Health Study. Clin Chem 2004;50:1364–71.

    Article  PubMed  CAS  Google Scholar 

  81. Koschinsky ML, Marcovina SM. Structure-function relationships in apolipoprotein(a): insights into lipoprotein(a) assembly and pathogenicity. Curr Opin Lipidol 2004;15:167–74.

    Article  PubMed  CAS  Google Scholar 

  82. Sangrar W, Bajzar L, Nesheim ME, Koschinsky ML. Antifibrinolytic effect of recombinant apolipoprotein(a) in vitro is primarily due to attenuation of tPA-mediated Glu-plasminogen activation. Biochemistry 1995; 34:5151–7.

    Article  PubMed  CAS  Google Scholar 

  83. Biemond BJ, Friederich PW, Koschinsky ML, Levi M, Sangrar W, Xia J, Buller HR, ten Cate JW. Apolipoprotein(a) attenuates endogenous fibrinolysis in the rabbit jugular vein thrombosis model in vivo. Circulation 1997;96:1612–5.

    PubMed  CAS  Google Scholar 

  84. Hancock MA, Boffa MB, Marcovina SM, Nesheim ME, Koschinsky ML. Inhibition of plasminogen activation by lipoprotein(a): critical domains in apolipoprotein(a) and mechanism of inhibition on fibrin and degraded fibrin surfaces. J Biol Chem 2003;278:23260–9.

    Article  PubMed  CAS  Google Scholar 

  85. Kojima S, Harpel PC, Rifkin DB. Lipoprotein (a) inhibits the generation of transforming growth factor beta: an endogenous inhibitor of smooth muscle cell migration. J Cell Biol 1991;113:1439–45.

    Article  PubMed  CAS  Google Scholar 

  86. Grainger DJ, Kirschenlohr HL, Metcalfe JC, Weissberg PL, Wade DP, Lawn RM. Proliferation of human smooth muscle cells promoted by lipoprotein(a). Science 1993;260:1655–8.

    Article  PubMed  CAS  Google Scholar 

  87. Grainger DJ, Kemp PR, Liu AC, Lawn RM, Metcalfe JC. Activation of transforming growth factor-beta is inhibited in transgenic apolipoprotein(a) mice. Nature 1994;370:460–2.

    Article  PubMed  CAS  Google Scholar 

  88. O’Neil CH, Boffa MB, Hancock MA, Pickering JG, Koschinsky ML. Stimulation of vascular smooth muscle cell proliferation and migration by apolipoprotein(a) is dependent on inhibition of transforming growth factor-beta activation and on the presence of kringle IV type 9. J Biol Chem 2004;279:55187–95.

    Article  PubMed  CAS  Google Scholar 

  89. Pellegrino M, Furmaniak-Kazmierczak E, LeBlanc JC, Cho T, Cao K, Marcovina SM, Boffa MB, Côté GP, Koschinsky ML. The apolipoprotein(a) component of lipoprotein(a) stimulates actin stress fiber formation and loss of cell-cell contact in cultured endothelial cells. J Biol Chem 2004;break 279:6526–33.

    Google Scholar 

  90. Allen S, Khan S, Tam S, Koschinsky M, Taylor P, Yacoub M. Expression of adhesion molecules by Lp(a): a potential novel mechanism for its atherogenicity. FASEB J 1998;12:1765–76.

    PubMed  CAS  Google Scholar 

  91. Schachinger V, Halle M, Minners J, Berg A, Zeiher AM. Lipoprotein(a) selectively impairs receptor-mediated endothelial vasodilator function of the human coronary circulation. J Am Coll Cardiol 1997;30:927–34.

    Article  PubMed  CAS  Google Scholar 

  92. Sotiriou SN, Orlova VV, Al-Fakhri N, Ihanus E, Economopoulou M, Isermann B, Bdeir K, Nawroth PP, Preissner KT, Gahmberg CG, et al. Lipoprotein(a) in atherosclerotic plaques recruits inflammatory cells through interaction with Mac-1 integrin. FASEB J 2006;20:559–61.

    PubMed  CAS  Google Scholar 

  93. Tsimikas S, Bergmark C, Beyer RW, Patel R, Pattison J, Miller E, Juliano J, Witztum JL. Temporal increases in plasma markers of oxidized low-density lipoprotein strongly reflect the presence of acute coronary syndromes. J Am Coll Cardiol 2003;41:360–70.

    Article  PubMed  CAS  Google Scholar 

  94. Tsimikas S, Lau HK, Han KR, Shortal B, Miller ER, Segev A, Curtiss LK, Witztum JL, Strauss BH. Percutaneous coronary intervention results in acute increases in oxidized phospholipids and lipoprotein(a). Circulation 2004;109:3164–70.

    Article  PubMed  CAS  Google Scholar 

  95. Edelstein C, Pfaffinger D, Hinman J, Miller E, Lipkind G, Tsimikas S, Bergmark C, Getz GS, Witztum JL, Scanu AM. Lysine-physphatidylcholine adducts in kringle V impart unique immunological and protein pro-inflammatory properties to human apolipoprotein(a). J Biol Chem 2003;278:52841–7.

    Article  PubMed  CAS  Google Scholar 

  96. Klezovitch O, Edelstein C, Scanu AM. Stimulation of interleukin-8 production in human THP-1 macrophages by apolipoprotein(a). Evidence for a critical involvement of elements in its C-terminal domain. J Biol Chem 2001;276:46864–9.

    Article  PubMed  CAS  Google Scholar 

  97. Kang C, Dominguez M, Loyau S, Miyata T, Durlach V, Anglés-Cano E. Lp(a) particles mold fibrin-binding properties of apo(a) in size-dependent manner: a study with different-length recombinant apo(a), native Lp(a), and monoclonal antibody. Arterioscler Thromb Vasc Biol 2002;22:1232–8.

    Article  PubMed  CAS  Google Scholar 

  98. Anglés-Cano E, de la Peña Díaz A, Loyau S. Inhibition of fibrinolysis by lipoprotein(a). Ann N Y Acad Sci 2001;936:261–75.

    Article  PubMed  Google Scholar 

  99. Knapp JP, Herrmann W. In vitro inhibition of fibrinolysis by apolipoprotein(a) and lipoprotein(a) is size- and concentration-dependent. Clin Chem Lab Med 2004;42:1013–9.

    Article  PubMed  CAS  Google Scholar 

  100. Boffa MB, Marcovina SM, Koschinsky ML. Lipoprotein(a) as a risk factor for atherosclerosis and thrombosis: mechanistic insights from animal models. Clin Biochem 2004;37:333–43.

    Article  PubMed  CAS  Google Scholar 

  101. Fan J, Shimoyamada H, Sun H, Marcovina S, Honda K, Watanabe T. Transgenic rabbits expressing human apolipoprotein(a) develop more extensive atherosclerotic lesion in response to a cholesterol-rich diet. Arterioscler Thromb Vasc Biol 2001;21:88–94.

    PubMed  CAS  Google Scholar 

  102. Sun H, Unoki H, Wang X, Liang J, Ichikawa T, Arai Y, Shiomi M, Marcovina SM, Watanabe T, Fan J. Lipoprotein(a) enhances advanced atherosclerosis and vascular calcification in WHHL transgenic rabbits expressing human apolipoprotein(a). J Biol Chem 2002;277:47486–92.

    Article  PubMed  CAS  Google Scholar 

  103. Guerra R, Yu Z, Marcovina S, Peshock R, Cohen JC, Hobbs HH. Lipoprotein(a) and apolipoprotein(a) isoforms: no association with coronary artery calcification in the Dallas Heart Study. Circulation 2005;111:1471–9.

    Article  PubMed  CAS  Google Scholar 

  104. Schneider M, Witztum JL, Young SG, Ludwig EH, Miller ER, Tsimikas S, Curtiss LK, Marcovina SM, Taylor JM, Lawn RM, et al. High-level lipoprotein(a) expression in transgenic mice: evidence for oxidized phospholipids in lipoprotein(a) but not in low density lipoproteins. J Lipid Res 2005;46:769–78.

    Article  PubMed  CAS  Google Scholar 

  105. Devlin CM, Lee SJ, Kuriakose G, Spencer C, Becker L, Grosskopf I, Ko C, Huang LS, Koschinsky ML, Cooper AD, et al. An apolipoprotein(a) peptide delays chylomicron remnant clearance and increases plasma remnant lipoproteins and atherosclerosis in vivo. Arterioscler Thromb Vasc Biol 2005;25:1704–10.

    Article  PubMed  CAS  Google Scholar 

  106. Yu KC, Cooper AD. Postprandial lipoproteins and atherosclerosis. Front Biosci 2001;6:D332–54.

    Article  PubMed  CAS  Google Scholar 

  107. Marcovina SM, Albers JJ, Scanu AM, Kennedy H, Giaculli F, Berg K, Couderc R, Dati F, Rifai N, Sakurabayashi I, et al. Use of a reference material proposed by the International Federation of Clinical Chemistry and Laboratory Medicine to evaluate analytical methods for the determination of plasma lipoprotein(a). Clin Chem 2000;46:1956–67.

    PubMed  CAS  Google Scholar 

  108. Tate JR, Berg K, Couderc R, Dati F, Kostner GM, Marcovina SM, Rifai N, Sakurabayashi I, Steinmetz A. International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) Standardization Project for the Measurement of Lipoprotein(a). Phase 2: selection and properties of a proposed secondary reference material for lipoprotein(a). Clin Chem Lab Med 1999;37:949–58.

    Article  PubMed  CAS  Google Scholar 

  109. Marcovina SM, Albers JJ, Gabel B, Koschinsky ML, Gaur VP. Effect of the number of apolipoprotein(a) kringle 4 domains on immunochemical measurements of lipoprotein(a). Clin Chem 1995;41:246–55.

    PubMed  CAS  Google Scholar 

  110. Dati F, Tate JR, Marcovina SM, Steinmetz A, International Federation of Clinical Chemistry and Laboratory Medicine, IFCC Working Group for Lipoprotein(a) Assay Standardization. First WHO/IFCC International Reference Reagent for Lipoprotein(a) for Immunoassay–Lp(a) SRM 2B. Clin Chem Lab Med 2004;42:670–6.

    Article  PubMed  CAS  Google Scholar 

  111. Edelstein C, Hinman J, Marcovina S, Scanu AM. Properties of human free apolipoprotein(a) and lipoprotein(a) after either freezing or lyophilization in the presence and absence of cryopreservatives. Anal Biochem 2001;288:201–8.

    Article  PubMed  CAS  Google Scholar 

  112. Scanu AM, Hinman J, Pfaffinger D, Edelstein C. Successful utilization of lyophilized lipoprotein(a) as a biological reagent. Lipids 2004;39:589–93.

    Article  PubMed  CAS  Google Scholar 

  113. Kulkarni KR, Garber DW, Marcovina SM, Segrest JP. Quantification of cholesterol in all lipoprotein classes by the VAP-II method. J Lipid Res 1994;35:159–68.

    PubMed  CAS  Google Scholar 

  114. Seman LJ, Jenner JL, MC Namara JR, Schaefer EJ. Quantification of lipoprotein(a) in plasma by assaying cholesterol in lectin – bound plasma fraction. Clin Chem 1994;40:400–3.

    Google Scholar 

  115. Baudhuin LM, Hartman SJ, O’Brien JF, Meissner I, Galen RS, Ward JN, Hogen SM, Branum EL, McConnell JP. Electrophoretic measurement of lipoprotein(a) cholesterol in plasma with and without ultracentrifugation: comparison with an immunoturbidimetric lipoprotein(a) method. Clin Biochem 2004;37:481–8.

    Article  PubMed  CAS  Google Scholar 

  116. Angelin B. Therapy for lowering lipoprotein (a) levels. Curr Opin Lipidol 1997;8:337–41.

    Article  PubMed  CAS  Google Scholar 

  117. Hobbs HH, White AL. Lipoprotein(a): intrigues and insights. Curr Opin Lipidol 1999;10:225–36.

    Article  PubMed  CAS  Google Scholar 

  118. Steyrer E, Durovic S, Frank S, Giessauf W, Burger A, Dieplinger H, Zechner R, Kostner GM. The role of lecithin: cholesterol acyltransferase for lipoprotein(a) assembly. Structural integrity of low density lipoproteins is a prerequisite for Lp(a) formation in human plasma. J Clin Invest 1994;94:2330–40.

    Article  PubMed  CAS  Google Scholar 

  119. White AL, Lanford RE. Biosynthesis and metabolism of lipoprotein(a). Curr Opin Lipidol 1995;6:75–80.

    PubMed  CAS  Google Scholar 

  120. Hrzenjak A, Frank S, Wo X, Zhou Y, Van Berkel T, Kostner GM. Galactose-specific asialoglycoprotein receptor is involved in lipoprotein (a) catabolism. Biochem J 2003;376:765–71.

    Article  PubMed  CAS  Google Scholar 

  121. Rahman MN, Becker L, Petrounevitch V, Hill BC, Jia Z, Koschinsky ML. Comparative analyses of the lysine binding site properties of apolipoprotein(a) kringle IV types 7 and 10. Biochemistry 2002;41:1149–55.

    Article  PubMed  CAS  Google Scholar 

Download references

Authors
  1. Michael B. Boffa PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Santica M. Marcovina PhD,ScD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Marlys L. Koschinsky PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Director of Preventive Cardiology, Rush University Medical Center Radiant Research, Chicago, IL

    Michael H. Davidson MD,FACC,FACP

  2. Director of Preventive Cardiology, Sterling Rock Falls Clinic Chief of Medicine CGH Medical Center Clinical Associate Professor, University of Illinois College of Medicine, Peoria, IL

    Peter P. Toth MD,PhD,FAAP,FICA,FAHA,FCCP,FACC

  3. Southern Illinois University School of Medicine, Springfield, IL

    Peter P. Toth MD,PhD,FAAP,FICA,FAHA,FCCP,FACC

  4. Chief Science Officer,Provident Clinical Research, Bloomington, IN

    Kevin C. Maki PhD

  5. Weill Cornell Medical College, New York, NY

    Antonio M. Gotto Jr MD,DPhil

Rights and permissions

Reprints and permissions

Copyright information

© 2007 Humana Press Inc.

About this chapter

Cite this chapter

Boffa, M.B., Marcovina, S.M., Koschinsky, M.L. (2007). Lipoprotein(a) as an Emerging Risk Factor for Atherothrombosis. In: Davidson, M.H., Toth, P.P., Maki, K.C., Gotto, A.M. (eds) Therapeutic Lipidology. Contemporary Cardiology. Humana Press. https://doi.org/10.1007/978-1-59745-533-6_12

Download citation

  • DOI: https://doi.org/10.1007/978-1-59745-533-6_12

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-551-4

  • Online ISBN: 978-1-59745-533-6

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation