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Thromb Haemost 1997; 77(06): 1077-1080
DOI: 10.1055/s-0038-1656115
Clinical Studies
Schattauer GmbH Stuttgart

Soluble P-selectin in Atherosclerosis: A Comparison with Endothelial Cell and Platelet Markers

Andrew D Blann
1   The City Hospital, Haemostasis, Thrombosis and Vascular Biology Unit, Univ. Dept of Medicine, Birmingham, UK
,
Gregory Y H Lip
1   The City Hospital, Haemostasis, Thrombosis and Vascular Biology Unit, Univ. Dept of Medicine, Birmingham, UK
,
D Gareth Beevers
2   Department of Medicine, The City Hospital, Birmingham, UK
,
Charles N McCollum
3   Department of Surgery, University Hospital of South, Didsbury, Manchester, UK
› Author Affiliations
Further Information

Publication History

Received 21 May 1996

Accepted after resubmission 13 February 1997

Publication Date:
12 July 2018 (online)

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Summary

von Willebrand factor and soluble thrombomodulin are established plasma markers of endothelial cell dysfunction, whilst beta thromboglobulin is an established plasma marker of platelet activity. Soluble P-selectin may be the product of either or both types of cell and levels of all four molecules have been previously found to be increased in atherosclerosis. To determine the relationship of soluble P-selectin to the endothelial cell and platelet products, we measured the four indices in a case control study of 55 patients with peripheral vascular disease and 55 age and sex matched controls, von Willebrand factor (p <0.0001), beta thromboglobulin (p = 0.0006), soluble P-selectin (p = 0.0021) and soluble thrombomodulin (p = 0.021) were all raised in the patients. Soluble P-selectin correlated with beta thromboglobulin (r = 0.34, p = 0.019) but failed to correlate with either endothelial cell marker. Co-culture of endothelial cells in vitro with bovine thrombin resulted in increased levels of von Willebrand factor in the supernatants but levels of soluble thrombomodulin and soluble P-selectin were not enhanced. Exposure of endothelial cell monolayers to elastase resulted in different patterns of release of von Willebrand factor, soluble thrombomodulin and soluble P-selectin. We suggest that soluble P-selectin is unlikely to arise from the endothelium and may be a new marker of platelet activation in atherosclerosis.

 

  • References

  • 1 Borsum T. Biochemical properties of vascular endothelial cells. Virchows Archiv B Cell Pathol 1991; 60: 279-286
    CrossrefPubMedGoogle Scholar
  • 2 Pober JS. Cytokine activation of vascular endothelium: physiology and pathology. Am J Pathol 1988; 113: 426-433
    PubMedGoogle Scholar
  • 3 Bevilacqua MP. Endothelial-leukocyte adhesion molecules. Annu Rev Immunol 1993; 11: 767-804
    CrossrefPubMedGoogle Scholar
  • 4 Blann AD, McCollum CN. von Willebrand factor, endothelial cell damage and atherosclerosis. Eur J Vase Surg 1994; 08: 10-15
    CrossrefPubMedGoogle Scholar
  • 5 Seigneur M, Dufourcq P, Conri C, Constans J, Mercie P, Pruvost A, Bois-seau M. Plasma thrombomodulin: new approach of endothelium damage. Int Angiology 1993; 12: 355-359
    PubMedGoogle Scholar
  • 6 Ross R. The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature 1993; 362: 801-809
    CrossrefPubMedGoogle Scholar
  • 7 Cahill MR, Newland AC. Platelet activation in coronary artery disease. Br J Biomed Sci 1993; 50: 221-234
    PubMedGoogle Scholar
  • 8 Rak K, Beck P, Udvardy M, Pfliegler G, Misz M, Boda Z. Plasma levels of beta thromboglobulin and factor VIII-related antigen in diabetic children and adults. Thromb Res 1983; 29: 155-162
    CrossrefPubMedGoogle Scholar
  • 9 Wagner DD. The Weibel-Palade body: the storage granule for von Willebrand factor and P-selectin. Thromb Haemost 1993; 70: 105-110
    Article in Thieme ConnectPubMedGoogle Scholar
  • 10 Niewiarowski S. Secreted platelet proteins. In ‘ Haemostasis and Thrombosis’. 03. rd edition Bloom AL, Forbes CD, Thomas DP, Tuddenham EGD. (eds) Edinburgh: Churchill Livingstone; 1994: 167-181
    Google Scholar
  • 11 Michelson AD, Barnard MR, Hechtman HB, MacGregor H, Connolly RJ, Valeri CR. Circulating degranulated platelets rapidly lose surface P-selectin but continue to circulate and function. Thromb Haemost 1995; 73: 1000 (abstract)
    PubMedGoogle Scholar
  • 12 Jilma B, Fasching P, Ruthner C, Rumplmayr A, Ruzicka S, Kapiotis S, Wagner OF, Eichler HG. Elevated circulating P-selectin in insulin dependent diabetes mellitus. Thromb Haemost 1996; 76: 328-332
    Article in Thieme ConnectPubMedGoogle Scholar
  • 13 Blann AD, Dobrotova M, Kubisz P, McCollum CN. von Willebrand factor, soluble P-selectin, tissue plasminogen activator and plasminogen activator inhibitor in atherosclerosis. Thromb Haemost 1995; 74: 626-630
    Article in Thieme ConnectPubMedGoogle Scholar
  • 14 Lip GY, Blann AD, Zarifis J, Beevers M, Lip PL, Beevers DG. Soluble adhesion molecule P-selectin and endothelial dysfunction in essential hypertension: implications for atherogenesis? A preliminary report. J Hypertension 1995; 13: 1674-1678
    PubMedGoogle Scholar
  • 15 Blann AD, Lip GYH. Hypothesis: Is soluble P-selectin a new marker of platelet activation. Atherosclerosis 1997; 128: 135-138
    CrossrefPubMedGoogle Scholar
  • 16 Booth F, Allington MJ, Cederholm-Williams SA. An in vitro model for the study of acute release of von Willebrand factor from human endothelial cells. BrJHaem 1987; 67: 71-78
    PubMedGoogle Scholar
  • 17 Chignard M, Balloy V, Renesto P. Leukocyte elastase-mediated release of von Willebrand factor from cultured endothelial cells. Eur Respir J 1993; 06: 791-796
    PubMedGoogle Scholar
  • 18 Jaffe EA, Hoyer LW, Nachman RL. Synthesis of antihemophilic factor antigen by cultured human endothelial cells. J Clin Invest 1973; 52: 2757-2764
    CrossrefPubMedGoogle Scholar
  • 19 Altman DG. Practical statistics for medical research. London: Chapman and Hall; 1991
    Google Scholar
  • 20 Seigneur M, Dufourcq P, Conri C, Constans J, Mercie P, Pruvost A, Amiral J, Midy D, Baste JC, Boisseau MR. Levels of plasma thrombomodulin are increased in atheromatous arterial disease. Thromb Res 1993; 71: 423-431
    CrossrefPubMedGoogle Scholar
  • 21 Giddings JC, Shall L. Enhanced release of von Willebrand factor by human endothelial cells in culture in the presence of phorbol myristate acetate and interleukin 1. Thromb Res 1987; 47: 259-267
    CrossrefPubMedGoogle Scholar
  • 22 Pottinger BE, Read RC, Paleolog EM, Higgins PG, Pearson JD. von Willebrand factor is an acute phase reactant in man. Thromb Res 1989; 53: 387-394
    CrossrefPubMedGoogle Scholar
  • 23 Jilma B, Hildebrandt J, Kapiotis S, Wagner OF, Kitzweger E, Mullner C, Monitzer B, Krejcy HG. Effects of estradiol on circulating P-selectin. J Clin Endocrinol Metab 1996; 81: 2350-2355
    PubMedGoogle Scholar
  • 24 Blann AD, Seigneur M, Adams R, McCollum CN. Neutrophil elastase, von Willebrand factor, soluble thrombomodulin and percutaneous oxygen in peripheral atherosclerosis. Eur J Vase Endovasc Surg 1996; 12: 218-222
    CrossrefPubMedGoogle Scholar
  • 25 Gando S, Nakanishi Y, Kameue T, Nanzaki S. Soluble thrombomodulin increases in patients with disseminated intravascular coagulation and in those with multiple organ dysfunction syndrome after trauma: role of neutrophil elastase. J Trauma 1995; 39: 660-664
    CrossrefPubMedGoogle Scholar
  • 26 Chong BH, Murray B, Berndt MC, Dunlop LC, Brighton T, Chesterman CN. Plasma P-selectin is increased in thrombotic consumptive platelet disorders. Blood 1994; 83: 1535-1541
    PubMedGoogle Scholar
  • 27 Berman CL, Yeo EL, Wencel-Drake JD, Furie BC, Ginsberg MH, Furie B. A platelet alpha granule membrane protein that is associated with the plasma membrane after activation. J Clin Invest 1986; 78: 130-137
    CrossrefPubMedGoogle Scholar
  • 28 Stenberg PE, McEver RP, Shuman MA, Jacques YV, Bainton DF. A platelet alpha-granule membrane protein (GMP-140) is expressed on the plasma membrane after activation. J Cell Biol 1986; 101: 880-886
    PubMedGoogle Scholar
  • 29 Katayama M, Handa M, Araki Y, Ambo H, Kawai Y, Watanabe K, Ikeda Y. Soluble P-selectin is present in normal circulation and its plasma levels is elevated in patients with thrombotic thrombocytopenic purpura and haemolytic uraemic syndrome. Br J Haem 1993; 84: 702-710
    CrossrefPubMedGoogle Scholar