Advertisement

American Journal of Pharmacogenomics

, Volume 3, Issue 5, pp 317–328 | Cite as

Genetic Polymorphisms in Cytokine and Adhesion Molecule Genes in Coronary Artery Disease

  • Johann AuerEmail author
  • Thomas Weber
  • Robert Berent
  • Eliabeth Lassnig
  • Gudrun Lamm
  • Bernd Eber
Genomics in Human Disease

Abstract

Both inflammation and genetics play an important role in the pathogenesis of atherosclerosis and coronary artery disease. Epidemiological studies have investigated the association between coronary artery disease (CAD) and gene polymorphisms of the inflammatory molecules tumor necrosis factors (TNF) α and β, transforming growth factors (TGF) β-1 and β-2, interleukin (IL)-1 and its receptor antagonist (IL-1ra), CD 14 (the receptor for lipopolysaccharide), P- and E-selectins, and platelet endothelial cell adhesion molecule (PECAM)-1.

Current evidence suggests that the TNF polymorphisms explored so far are not linked to CAD. The majority of studies conducted showed no significant association between TGFβ-1 and coronary atherosclerosis, but the data currently available are somewhat controversial. Some polymorphisms may increase the risk of myocardial infarction (MI) within specific ethnic groups or in certain populations. The association between the IL-1 system and atherosclerosis is complex and may vary as a result of a number of factors, such as stage of disease, clinical phenotype, and possibly population characteristics.

The E-selectin gene (SELE) Arg128, 98T, and Phe554 alleles may increase the risk of atherosclerosis, but not necessarily the risk of MI. This association seems to be more pronounced in younger patients. The PECAM1 Leu125Val and Ser563Asn polymorphisms may increase the risk of atherosclerosis but not necessarily of MI. This association may be especially important in patients with a low risk for developing atherosclerosis.

Current data indicate that screening for CD14-260C/T genotypes is unlikely to be a useful tool for risk assessment and it remains unclear whether CD14 polymorphisms significantly increase the risk of MI.

The associations between candidate gene polymorphisms and CAD are complex as a consequence of pleiotropy, variations with age, selection due to the high lethality of the disease, and interactions with other genes and environmental factors. Nonetheless, although the current data is preliminary and partly conflicting, it does provide some evidence that alterations in the genetics of the inflammatory system may modify the risk of CAD.

Keywords

Coronary Artery Disease Coronary Atherosclerosis Platelet Endothelial Cell Adhesion Molecule Major Histocompatibility Complex Haplotype Tumor Necrosis Factor Gene 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

The authors have provided no information on sources of funding or on conflicts of interest directly relevant to the content of this review.

References

  1. 1.
    Kannel WB. Overview of atherosclerosis. Clin Ther 1998; 20Suppl. B: B2–B17PubMedCrossRefGoogle Scholar
  2. 2.
    Verschuren WM, Jacobs DR, Bloemberg BP, et al. Serum total cholesterol and long-term coronary heart disease mortality in different cultures: twenty-five-year follow-up of the Seven Countries Study. JAMA 1995; 274: 131–6PubMedCrossRefGoogle Scholar
  3. 3.
    Ross R. Atherosclerosis: an inflammatory disease. N Engl J Med 1999; 340: 115–26PubMedCrossRefGoogle Scholar
  4. 4.
    Epstein SE, Zhou YF, Zhu J. Infection and atherosclerosis: emerging mechanistic paradigms. Circulation 1999; 100: e20–8PubMedCrossRefGoogle Scholar
  5. 5.
    Woods A, Brull DJ, Humphries SE, et al. Genetics of inflammation and risk of coronary artery disease: the central role of interleukin-6. Eur Heart J 2000; 21: 1574–83PubMedCrossRefGoogle Scholar
  6. 6.
    Mattila KJ, Valtonen VV, Nieminen MS. Role of infection as a risk factor for atherosclerosis, myocardial infarction, and stroke. Clin Infect Dis 1998; 26: 719–34PubMedCrossRefGoogle Scholar
  7. 7.
    Muhlestein JB. Chronic infection and coronary artery disease. Med Clin North Am 2000; 84: 123–48PubMedCrossRefGoogle Scholar
  8. 8.
    Libby P, Egan D, Skarlatos S. Roles of infectious agents in atherosclerosis and restenosis: an assessment of the evidence and need for future research. Circulation 1997; 96: 4095–103PubMedCrossRefGoogle Scholar
  9. 9.
    Auer J, Berent R, Weber T, et al. Immunopathogenesis of atherosclerosis. Circulation 2002; 105: E64PubMedGoogle Scholar
  10. 10.
    Eldor A, Sela-Donenfeld D, Korner M, et al. Injury models of the vascular endothelium: apoptosis and loss of thromboresistance induced by a viral protein. Haemostasis 1996; 26Suppl. 4: 37–45PubMedGoogle Scholar
  11. 11.
    Etingin OR, Silverstein RL, Friedman HM, et al. Viral activation of the coagulation cascade: molecular interactions at the surface of infected endothelial cells. Cell 1990; 61: 657–62PubMedCrossRefGoogle Scholar
  12. 12.
    Ikonomidis I, Andreotti F, Economou E, et al. Increased proinflammatory cytokines in patients with chronic stable angina and their reduction by aspirin. Circulation 1999; 100: 793–8PubMedCrossRefGoogle Scholar
  13. 13.
    Auer J, Berent R, Lassnig E, et al. Serum neopterin and activity of coronary artery disease. Heart Dis 2001; 3: 297–301PubMedCrossRefGoogle Scholar
  14. 14.
    Auer J, Berent R, Lassnig E, et al. Prognostic significance of immune activation after acute coronary syndromes [letter]. J Am Coll Cardiol 2002; 39: 1878PubMedCrossRefGoogle Scholar
  15. 15.
    Auer J, Rammer M, Berent R, et al. Relation of C-reactive protein levels to presence, extent, and severity of angiographic coronary artery disease. Indian Heart J 2002; 54: 284–8PubMedGoogle Scholar
  16. 16.
    Auer J, Berent R, Lassnig E, et al. C-reactive protein and coronary artery disease. Jpn Heart J 2002; 43: 607–19PubMedCrossRefGoogle Scholar
  17. 17.
    Auer J, Berent R, Weber T, et al. Cytokine gene polymorphisms and development of CAD associated with CP infection. J Am Coll Cardiol 2002; 39: 918–9PubMedCrossRefGoogle Scholar
  18. 18.
    Andreotti F, Porto I, Crea F, et al. Inflammatory gene polymorphisms and ischaemic heart disease: review of population association studies. Heart 2002; 87: 107–12PubMedCrossRefGoogle Scholar
  19. 19.
    Manzoli A, Andreotti F, Varlotta C, et al. Allelic polymorphism of the interleukin-1 receptor antagonist gene in patients with acute or stable presentation of ischemic heart disease. Cardiologia 1999; 44: 825–30PubMedGoogle Scholar
  20. 20.
    Iacoviello L, Donati MB, Gattone M. Possible different involvement of interleukin-1 receptor antagonist gene polymorphism in coronary single vessel disease and myocardial infarction [letter]. Circulation 2000; 101(18): E193PubMedCrossRefGoogle Scholar
  21. 21.
    Hubacek JA, Pit’ha J, Skodova Z, et al. C(-260)T polymorphism in the promoter of the CD 14 monocyte receptor gene as a risk factor for myocardial infarction. Circulation 1999; 99: 3218–20PubMedCrossRefGoogle Scholar
  22. 22.
    Shimada K, Watanabe Y, Mokuno H, et al. Common polymorphism in the promoter of the CD14 monocyte receptor gene is associated with acute myocardial infarction in Japanese men. Am J Cardiol 2000; 86: 682–4PubMedCrossRefGoogle Scholar
  23. 23.
    Unkelbach K, Gardemann A, Kostrzewa M, et al. A new promoter polymorphism in the gene of lipopolysaccharide receptor CD14 is associated with expired myocardial infarction in patients with low atherosclerotic risk profile. Arterioscler Thromb Vasc Biol 1999; 19: 932–8PubMedCrossRefGoogle Scholar
  24. 24.
    Zee RYL, Lindpaintner K, Struk B, et al. A prospective evaluation of the CD14 C(−260)T gene polymorphism and the risk of myocardial infarction. Atherosclerosis 2001; 154: 699–702PubMedCrossRefGoogle Scholar
  25. 25.
    Herrmann SM, Ricard S, Nicaud V, et al. The P-selectin gene is highly polymorphic: reduced frequency of the Pro715 carriers in patients with myocardial infarction. Hum Mol Genet 1998; 7: 1277–84PubMedCrossRefGoogle Scholar
  26. 26.
    Gardemann A, Knapp A, Katz N, et al. No evidence for the CD31 C/G gene polymorphism as an independent risk factor of coronary heart disease [letter]. Thromb Haemost 2000; 83: 629PubMedGoogle Scholar
  27. 27.
    Herrmann SM, Ricard S, Nicaud V, et al. Polymorphisms of the tumor necrosis factor-alpha gene, coronary heart disease and obesity. Eur J Clin Invest 1998; 28: 59–66PubMedCrossRefGoogle Scholar
  28. 28.
    Padovani JC, Pazin-Filho A, Simoes MV, et al. Gene polymorphisms in the TNF locus and the risk of myocardial infarction. Thromb Res 2000; 100: 263–9PubMedCrossRefGoogle Scholar
  29. 29.
    Cambien F, Richard S, Troesch A, et al. Polymorphism of the transforming growth factor-β1 gene in relation to myocardial infarction and blood pressure: the Etude Cas-Temoin de l’Infarctus du Myocarde (ECTIM) study. Hypertension 1996; 28: 881–7PubMedCrossRefGoogle Scholar
  30. 30.
    Francis SE, Camp NJ, Dewberry RM, et al. Interleukin-1 receptor antagonist gene polymorphism and coronary artery disease. Circulation 1999; 99: 861–6PubMedCrossRefGoogle Scholar
  31. 31.
    Kastrati A, Koch W, Berger P, et al. Protective role against restenosis from an interleukin-1 receptor antagonist gene polymorphism in patients treated with coronary stenting. J Am Coll Cardiol 2000; 36: 2168–73PubMedCrossRefGoogle Scholar
  32. 32.
    Wenzel K, Felix S, Kleber FX, et al. E-selectin polymorphism and atherosclerosis: an association study. Hum Mol Genet 1994; 3: 1935–7PubMedCrossRefGoogle Scholar
  33. 33.
    Wenzel K, Ernst M, Rohde K, et al. DNA polymorphisms in adhesion molecule genes: a new risk factor for early atherosclerosis. Hum Genet 1996; 97: 15–20PubMedCrossRefGoogle Scholar
  34. 34.
    Ye SQ, Usher D, Virgil D, et al. A PstI polymorphism detects the mutation of serinel28 to arginine in CD 62E gene: a risk factor for coronary artery disease. J Biomed Sci 1999; 6: 18–21PubMedGoogle Scholar
  35. 35.
    Wenzel K, Baumann G, Felix SB. The homozygous combination of Leu 125Val and Ser563Asn polymorphisms in the PECAM1 gene (CD31) is associated with early severe coronary heart disease. Hum Mutat 1999; 14: 545PubMedCrossRefGoogle Scholar
  36. 36.
    Keso T, Perola M, Laippala P, et al. Polymorphisms within the tumor necrosis factor locus and prevalence of coronary artery disease in middle-aged men. Atherosclerosis 2001; 154: 691–7PubMedCrossRefGoogle Scholar
  37. 37.
    Braun J, Marz W, Winkelmann BR, et al. Tumor necrosis factor β alleles and hyperinsulinaemia in coronary artery disease. Eur J Clin Invest 1998; 28: 538–42PubMedCrossRefGoogle Scholar
  38. 38.
    Syrris P, Carter ND, Metcalfe JC, et al. Transforming growth factor-beta1 gene polymorphisms and coronary artery disease. Clin Sci 1998; 95: 659–67PubMedCrossRefGoogle Scholar
  39. 39.
    Wang XL, Sim AS, Wilcken DEL. A common polymorphism of the transforming growth factor β 1 gene and coronary artery disease. Clin Sci 1998; 95: 745–6PubMedCrossRefGoogle Scholar
  40. 40.
    Biggart S, Chin D, Fauchon M, et al. Association of genetic polymorphisms in the ACE, ApoE, and TGF beta genes with early onset ischemic heart disease. Clin Cardiol 1998; 21: 831–6PubMedCrossRefGoogle Scholar
  41. 41.
    Vassalli P. The pathophysiology of tumor necrosis factors. Annu Rev Immunol 1992; 10: 411–52PubMedCrossRefGoogle Scholar
  42. 42.
    Azzawi M, Hasleton P. Tumor necrosis factor alpha and the cardiovascular system: its role in cardiac allograft rejection and heart disease. Cardiovasc Res 1999; 43: 850–9PubMedCrossRefGoogle Scholar
  43. 43.
    Azzawi M, Hasleton PS, Hutchinson IV. TNF-alpha in acute cardiac transplant rejection. Cytokines Cell Mol Ther 1999; 5: 41–9PubMedGoogle Scholar
  44. 44.
    Azzawi M, Hasleton PS, Turner DM, et al. Tumor necrosis factor-alpha gene polymorphism and death due to acute cellular rejection in a subgroup of heart transplant recipients. Hum Immunol 2001; 62: 140–2PubMedCrossRefGoogle Scholar
  45. 45.
    Wilson AG, Symons JA, McDowell TL, et al. Effects of a polymorphism in the human tumor necrosis factor alpha promoter on transcriptional activation. Proc Natl Acad Sci U S A 1997; 94: 3195–9PubMedCrossRefGoogle Scholar
  46. 46.
    Jacob CO. Tumor necrosis factor alpha in autoimmunity: pretty girl or old witch? Immunol Today 1992; 13: 122–5PubMedCrossRefGoogle Scholar
  47. 47.
    DiGiovine FS, Nuki G, Duff GW. Tumor necrosis factor in synovial exudates. Ann Rheum Dis 1988; 47: 768–72PubMedCrossRefGoogle Scholar
  48. 48.
    Kwiatkowski D, Hill AVS, Sambou I, et al. TNF concentration in fatal cerebral, non-fatal cerebral, and uncomplicated Plasmodium falciparum malaria. Lancet 1990; 336: 1201–4PubMedCrossRefGoogle Scholar
  49. 49.
    Jacob CO, Fronek Z, Lewis GD, et al. Heritable major histocompatibility complex class II-associated differences in production of tumor necrosis factor alpha: relevance to genetic predisposition to systemic lupus erythematosus. Proc Natl Acad Sci U S A 1990; 87: 1233–7PubMedCrossRefGoogle Scholar
  50. 50.
    Abraham LJ, French MAH, Dawkins RL. Polymorphic MHC ancestral haplotypes affect the activity of tumor necrosis factor-alpha. Clin Exp Immunol 1993; 92: 14–8PubMedCrossRefGoogle Scholar
  51. 51.
    Bendtzen K, Morling N, Fomsgaard A, et al. Association between HLA-DR2 and production of tumor necrosis factor alpha and interleukin 1 by mononuclear cells activated by lipopolysaccharide. Scand J Immunol 1988; 28: 599–606PubMedCrossRefGoogle Scholar
  52. 52.
    Jongeneel CV, Acha-Orbea H, Blankenstein T. A polymorphic microsatellite in the tumor necrosis factor alpha promoter identifies an allele unique to the NZW mouse strain. J Exp Med 1990; 171: 2141–6PubMedCrossRefGoogle Scholar
  53. 53.
    Beutler B, Brown T. Polymorphism of the mouse TNF-alpha locus: sequence studies of the 3’-untranslated region and first intron. Gene 1993; 129: 279–83PubMedCrossRefGoogle Scholar
  54. 54.
    Jacob CO, Hwang F, Lewis GD, et al. Tumor necrosis factor alpha in murine systemic lupus erythematosus disease models: implications for genetic predisposition and immune regulation. Cytokine 1991; 3: 551–6PubMedCrossRefGoogle Scholar
  55. 55.
    Wilson AG, Di Giovine FS, Blakemore AIF, et al. Single base polymorphism in the human tumor necrosis factor alpha (TNF alpha) gene detectable by NcoI restriction of PCR product. Hum Mol Genet 1992; 1: 353PubMedCrossRefGoogle Scholar
  56. 56.
    D’Alfonso S, Momigliano-Richiardi P. A polymorphic variation in a putative regulation box of the TNFA promoter region. Immunogenetics 1994; 39: 150–4PubMedGoogle Scholar
  57. 57.
    Wilson AG, De Vries N, Pociot F, et al. An allelic polymorphism within the human tumor necrosis factor alpha promoter region is strongly associated with HLA A1, B8, and DR3 alleles. J Exp Med 1993; 177: 557–60PubMedCrossRefGoogle Scholar
  58. 58.
    Koch W, Kastrati A, Bottiger C, et al. Interleukin-10 and tumor necrosis factor gene polymorphisms and risk of coronary artery disease and myocardial infarction. Atherosclerosis 2001; 159: 137–44PubMedCrossRefGoogle Scholar
  59. 59.
    Massague J. TGF-β signal transduction. Annu Rev Biochem 1998; 67: 753–91PubMedCrossRefGoogle Scholar
  60. 60.
    Grainger DJ, Kemp PR, Liu AC, et al. Activation of transforming growth factor-β is inhibited in transgenic apolipoprotein(a) mice. Nature 1994; 370: 460–2PubMedCrossRefGoogle Scholar
  61. 61.
    Grainger DJ, Witchell CM, Metcalfe JC. Tamoxifen elevates transforming growth factor-β and suppresses diet-induced formation of lipid lesions in mouse aorta. Nat Med 1995; 1: 1067–73PubMedCrossRefGoogle Scholar
  62. 62.
    McDonald CC, Alexander FE, Whyte BW, et al. Cardiac and vascular morbidity in women receiving adjuvant tamoxifen for breast cancer in a randomised trial. BMJ 1995; 311: 977–80PubMedCrossRefGoogle Scholar
  63. 63.
    McCaffrey TA, Consigli S, Du B, et al. Decreased type II/type I TGF-β receptor ratio in cells derived from human atherosclerotic lesions: conversion from an antiproliferative to profibrotic response to TGF-β1. J Clin Invest 1995; 96: 2667–75PubMedCrossRefGoogle Scholar
  64. 64.
    McCaffrey TA, Du B, Consigli S, et al. Genomic instability in the type II TGF-β1 receptor gene in atherosclerotic and restenotic vascular cells. J Clin Invest 1997; 100: 2182–8PubMedCrossRefGoogle Scholar
  65. 65.
    McCaffrey TA, Du B, Fu C, et al. The expression of TGF-β receptors in human atherosclerosis: evidence for acquired resistance to apoptosis due to receptor imbalance. J Mol Cell Cardiol 1999; 31: 627–42CrossRefGoogle Scholar
  66. 66.
    Nikol S, Isner JM, Pickering JG, et al. Expression of transforming growth factor-beta 1 is increased in human vascular restenosis lesions. J Clin Invest 1992; 90: 1582–92PubMedCrossRefGoogle Scholar
  67. 67.
    Francis SE, Camp NJ, Dewberry RM, et al. Interleukin-1 receptor antagonist gene polymorphism and coronary artery disease. Circulation 1999; 99: 861–6PubMedCrossRefGoogle Scholar
  68. 68.
    diGiovine FS, Duff GW. Interleukin-1: the first interleukin. Immunol Today 1990; 11: 13–20PubMedCrossRefGoogle Scholar
  69. 69.
    Ikonomidis I, Andreotti F, Economou E, et al. Increased proinflammatory cytokines in patients with chronic stable angina and their reduction by aspirin. Circulation 1999; 100: 793–8PubMedCrossRefGoogle Scholar
  70. 70.
    Dinarello CA. Interleukin 1 and interleukin 1 receptor antagonism. Blood 1991; 77: 1627–52PubMedGoogle Scholar
  71. 71.
    Galea J, Armstrong JA, Gadsdon PA, et al. Interleukin-1β in coronary arteries of patients with ischemic heart disease. Arterioscler Thromb Vasc Biol 1996; 16: 1000–6PubMedCrossRefGoogle Scholar
  72. 72.
    Bochner BS, Luscinskas FW, Gimbrone Jr MA, et al. Adhesion of human basophils, eosinophils, and neutrophils to interleukin-1 activated endothelial cells: contributions of endothelial cell adhesion molecules. J Exp Med 1991; 173: 1553–7PubMedCrossRefGoogle Scholar
  73. 73.
    Bevilacqua MP, Pober S, Majeau GR, et al. Interleukin-1 induces biosynthesis and cell surface expression of procoagulant activity in human vascular endothelial cells. J Exp Med 1984; 160: 618–23PubMedCrossRefGoogle Scholar
  74. 74.
    Offner FA, Feichtinger H, Stadlmann S, et al. TGF-β synthesis in human peritoneal cells: induction by IL-1. Am J Pathol 1996; 148: 1679–88PubMedGoogle Scholar
  75. 75.
    Auer J, Berent R, Weber T, et al. Interleukin-1 receptor antagonist gene polymorphism, infectious burden, and coronary artery disease. Clin Infect Dis 2002; 34: 1536–7PubMedCrossRefGoogle Scholar
  76. 76.
    Ikeda U, Ito T, Shimada K. Interleukin-6 and acute coronary syndrome. Clin Cardiol 2001; 24: 701–4PubMedCrossRefGoogle Scholar
  77. 77.
    Vickers MA, Green FR, Terry C, et al. Genotype at a promoter polymorphism of the interleukin-6 gene is associated with baseline levels of plasma C-reactive protein. Cardiovasc Res 2002; 53: 1029–34PubMedCrossRefGoogle Scholar
  78. 78.
    Nauck M, Winkelmann BR, Hoffmann MM, et al. The interleukin-6 G(-174)C promoter polymorphism in the LURIC cohort: no association with plasma interleukin-6, coronary artery disease, and myocardial infarction. J Mol Med 2002; 80: 507–13PubMedCrossRefGoogle Scholar
  79. 79.
    Brull DJ, Montgomery HE, Sanders J, et al. Interleukin-6 gene −174g>c and −572g>c promoter polymorphisms are strong predictors of plasma interleukin-6 levels after coronary artery bypass surgery. Arterioscler Thromb Vasc Biol 2001; 21: 1458–63PubMedCrossRefGoogle Scholar
  80. 80.
    Hogg N, Landis RC. Adhesion molecules in cell interaction. Curr Opin Immunol 1993; 5: 383–90PubMedCrossRefGoogle Scholar
  81. 81.
    Ikeda H, Takajo Y, Ichiki K, et al. Increased soluble form of P-selectin in patients with unstable angina. Circulation 1995; 92: 1693–6PubMedCrossRefGoogle Scholar
  82. 82.
    Johnston GI, Bliss BA, Newman PJ, et al. Structure of the human gene encoding granule membrane protein-140, a member of the selectin family of the adhesion receptors for leukocytes. J Biol Chem 1990; 265: 21381–5PubMedGoogle Scholar
  83. 83.
    Kee F, Morrison C, Evans AE, et al. Polymorphisms of the P-selectin gene and risk of myocardial infarction in men and women in the ECTIM extension study. Heart 2000; 84: 548–52PubMedCrossRefGoogle Scholar
  84. 84.
    Paysant JR, Rupin A, Verbeuren TJ. Effect of NADPH oxidase inhibition on E-selectin expression induced by concomitant anoxia/reoxygenation and TNF-alpha. Endothelium 2002; 9: 263–71PubMedCrossRefGoogle Scholar
  85. 85.
    Pober JS, Bevilacqua MP, Mendrick DL, et al. Two distinct monokines, interleukin 1 and tumor necrosis factor, each independently induce biosynthesis and transient expression of the same antigen on the surface of cultured human vascular endothelial cells. J Immunol 1986; 136: 1680–7PubMedGoogle Scholar
  86. 86.
    Wenzel K, Stahn R, Speer A, et al. Functional characterization of atherosclerosis-associated Serl28Arg and Leu554Phe E-selectin mutations. Biol Chem 1999; 380: 661–7PubMedCrossRefGoogle Scholar
  87. 87.
    Serebruany VL, Murugesan SR, Pothula A, et al. Soluble PECAM-1, but not P-selectin, nor osteonectin identify acute myocardial infarction in patients presenting with chest pain. Cardiology 1999; 91: 50–5PubMedCrossRefGoogle Scholar
  88. 88.
    Gumina RJ, Kirschbaum NE, Rao PN, et al. The human PECAM1 gene maps to 17q23. Genomics 1996; 34: 229–32PubMedCrossRefGoogle Scholar
  89. 89.
    Wright SD, Ramos RA, Tobias PS, et al. CD14, a receptor for complexes of lipopolysaccharide (LPS) and LPS binding protein. Science 1990; 249: 1431–3PubMedCrossRefGoogle Scholar
  90. 90.
    Liao W. Endotoxin: possible roles in initiation and development of atherosclerosis. J Lab Clin Med 1996; 128: 452–60PubMedCrossRefGoogle Scholar
  91. 91.
    Loppnow H, Stelter F, Schonbeck U, et al. Endotoxin activates human vascular smooth muscle cells despite lack of expression of CD14 mRNA or endogenous membrane CD14. Infect Immun 1995; 63: 1020–6PubMedGoogle Scholar
  92. 92.
    Lane DA, Grant PJ. Role of hemostatic gene polymorphisms in venous and arterial thrombotic disease. Blood 2000; 95: 1517–32PubMedGoogle Scholar

Copyright information

© Adis Data Information BV 2003

Authors and Affiliations

  • Johann Auer
    • 1
    Email author
  • Thomas Weber
    • 1
  • Robert Berent
    • 1
  • Eliabeth Lassnig
    • 1
  • Gudrun Lamm
    • 1
  • Bernd Eber
    • 1
  1. 1.Department of Internal Medicine II, Division of Cardiology and Intensive CareGeneral Hospital WelsWelsAustria

Personalised recommendations