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Thromb Haemost 1991; 66(05): 581-585
DOI: 10.1055/s-0038-1646463
Original Article
Schattauer GmbH Stuttgart

Plasminogen Activators t-PA, u-PA and Its Inhibitor (PAI) in Normal Males and Females

Stephen C L Koh
National University of Singapore, Department of Obstetrics and Gynaecology, National University Hospital, Singapore
,
R Yuen
National University of Singapore, Department of Obstetrics and Gynaecology, National University Hospital, Singapore
,
O A C Viegas
National University of Singapore, Department of Obstetrics and Gynaecology, National University Hospital, Singapore
,
S E Chua
National University of Singapore, Department of Obstetrics and Gynaecology, National University Hospital, Singapore
,
B L Ng
National University of Singapore, Department of Obstetrics and Gynaecology, National University Hospital, Singapore
,
D K Sen
National University of Singapore, Department of Obstetrics and Gynaecology, National University Hospital, Singapore
,
S S Ratnam
National University of Singapore, Department of Obstetrics and Gynaecology, National University Hospital, Singapore
› Author Affiliations
Further Information

Publication History

Received 08 March 1990

Accepted 07 May 1991

Publication Date:
25 July 2018 (online)

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Summary

We determined the plasma levels of tissue plasminogen activator (t-PA), plasminogen activator inhibitor (PAI) activity and their antigen levels including urokinase plasminogen activator (u-PA) in 33 male and 27 female normal subjects. Males had mean t-PA activity of 0.50 iu/ml which was significantly lower (p <0.01) than the females 0.64 iu/ml. Males had higher (p <0.001) mean PAI activity (15.5 AU/ml) as compared to females 10.3 AU/ml. The respective mean levels of t-PA and PAI antigen were significantly higher (p <0.01) in males (8.1 ng/ml and 17.6 ng/ml) than in females (6.2 ng/ml and 12.1 ng/ml). The mean u-PA level in males was 1.54 ng/ml which was significantly higher (p <0.01) than in females with 1.02 ng/ml. In post-venous occlusion studies, females had a greater mean response of 8.6 fold in t-PA activity as compared to males with a mean of 4.5 fold increase. The mean t-PA antigen response in males was 2.0 fold increase as compared to 2.6 fold increase in the females. No significant responses were seen in both sexes in either PAI activity or antigen levels when compared with the resting state. In zymography studies, free t-PA, its inhibitor complexes and u-PA were demonstrated in the euglobulin fractions of stored plasma. This study demonstrates that significant differences in t-PA, u-PA and PAI exist between male and female subjects which should be taken into account when determining their levels in clinical conditions.

 

  • References

  • 1 Wun TC, Capuano A. Initiation and regulation of fibrinolysis in human plasma and the plasminogen activator level. Blood 1987; 69: 1354-62
    PubMedSearch in Google Scholar
  • 2 Gilboa N, Kaplan JE. Plasma fibronectin enhances fibrinolytic system in vitro. Thromb Haemostas 1985; 54: 639-44
    PubMedSearch in Google Scholar
  • 3 Ranby M, Bergsdorf N, Nilsson T, Mellbring G, Winblad B, Bucht G. Age dependence of tissue plasminogen activator concentration in plasma, as studied by an improved Enzyme-Linked Immunosorbent Assay. Clin Chem 1986; 32: 2160-5
    PubMedSearch in Google Scholar
  • 4 Krishnamurti C, Tang DB, Barr CF. Plasminogen activator and plasminogen activator inhibitor activities in a reference population. Am J Clin Pathol 1988; 89: 747-52
    CrossrefPubMedSearch in Google Scholar
  • 5 Wijngaards G, Kluft G, Groeneveld E. Demonstration of urokinase-related fibrinolytic activity in human plasma. Br J Haematol 1982; 51: 165-9
    CrossrefPubMedSearch in Google Scholar
  • 6 Wun TC, Schleuning WD, Reich E. Isolation and characterization of urokinase in plasma. J Biol Chem 1982; 257: 3276-83
    PubMedSearch in Google Scholar
  • 7 Kristensen P, Larson L-I, Nielsen L, Grondahl-Hansen J, Andreasen PA, Dano K. Human endothelial cells contain one type of plasminogen activator. FEBS 1984; 168: 33-7
    CrossrefPubMedSearch in Google Scholar
  • 8 Koh Stephen CL, Yuen R, Viegas OAC, Chua SE, Ng BL, Sen DK, Ratnam SS. A plasmin generation method for the determination of tissue plasminogen activator (t-PA) activity in blood. Immunol Cell Biol 1989; 67: 197-203
    CrossrefPubMedSearch in Google Scholar
  • 9 Koh Stephen CL, Yuen R, Viegas OAC, Chua SE, Ng BL, Sen DK, Ratnam SS. Plasma tissue plasminogen activator inhibitor (t-PAI) activity in normal subjects. Med Sci Res 1989; 17: 135-6
    PubMedSearch in Google Scholar
  • 10 Granelli-Piperno A, Reich E. A study of proteases and proteases inhibitor complexes in biological fluids. J Exp Med 1978; 148: 223-34
    CrossrefPubMedSearch in Google Scholar
  • 11 Koh Stephen CL, Wong PC, Yuen R, Chua SE, Ng BL, Ratnam SS. Plasminogen activators in the endometrium of subfertile women. Med Sci Res 1988; 16: 1111-2
    PubMedSearch in Google Scholar
  • 12 Booth NA, Walker E, Maugham R, Bennett B. Plasminogen activator in normal subjects after exercise and venous occlusion, t-PA circulates as complexes with C1-inhibitor and RAM. Blood 1987; 69: 1600-4
    PubMedSearch in Google Scholar
  • 13 Pannell R, Gurewich V. Pro-urokinase - a study of its stability in plasma and of a mechanism for its selective fibrinolytic effect. Blood 1986; 67: 1215-23
    PubMedSearch in Google Scholar
  • 14 Bergsdorf N, Nilsson T, Wallen P. An enzyme-linked immunoassay for determination of tissue plasminogen activator applied to patients with thromboembolic disease. Thromb Haemostas 1983; 50: 740-4
    PubMedSearch in Google Scholar
  • 15 Wiman B, Ljunberg B, Chmielewska J, Urden G, Blombôck M, Johnsson H. The role of the fibrinolytic system in deep vein thrombosis. J Lab Clin Med 1985; 105: 265-70
    PubMedSearch in Google Scholar
  • 16 Nilsson UM, Ljungner H, Tengborn L. Two different mechanisms in patients with venous thrombosis and defective fibrinolysis – low concentration of plasminogen activator or increase concentration of plasminogen activator inhibitor. Br Med J 1985; 290: 1453-5
    CrossrefPubMedSearch in Google Scholar
  • 17 Johnsson O, Mellbring G, Nilsson T. Defective fibrinolysis in survivors of myocardial infarction. Int J Cardiol 1984; 6: 380-2
    CrossrefPubMedSearch in Google Scholar
  • 18 Hamsten A, Wiman B, deFaire U, Blombôck M. Increased plasma levels of a rapid inhibitor of tissue plasminogen activator in young survivors of myocardial infarction. N Engl J Med 1985; 313: 1557-63
    CrossrefPubMedSearch in Google Scholar
  • 19 Holvoet P, Cleemput H, Collen D. Assay of human tissue-type plasminogen activator (t-PA) with an enzyme-linked immunosorbent assay (ELISA) based on three murine monoclonal antibodies to t-PA. Thromb Haemostas 1985; 54: 684-7
    PubMedSearch in Google Scholar
  • 20 Wiman B, Mellbring G, Ranby M. Plasminogen activator release during venous stasis and exercise as determined by a new specific assay. Clin Chim Acta 1983; 127: 279-88
    CrossrefPubMedSearch in Google Scholar
  • 21 Levin RI, Harpel PC, Weil D, Chang TS, Rifkin DB. Aspirin inhibits vascular plasminogen activator activity in vivo. J Clin Invest 1984; 74: 571-80
    CrossrefPubMedSearch in Google Scholar
  • 22 Campbell EE, Shifman MA, Lewis JG, Pasqua JJ, Pizzo SV. A colorimetric assay for releaseable plasminogen activator. Clin Chem 1982; 28: 1125-8
    PubMedSearch in Google Scholar
  • 23 Hammouda MW, Moroz LA. Aspirin and venous occlusion: Effects on blood fibrinolytic activity and tissue plasminogen activator levels. Thromb Res 1986; 42: 73-82
    CrossrefPubMedSearch in Google Scholar
  • 24 Williams RS, Logue EE, Lewis JL, Barton T, Stead NW, Wallace AG, Pizzo SV. Physical conditioning augments the fibrinolytic response to venous occlusion in healthy adults. N Engl J Med 1980; 302: 987-91
    CrossrefPubMedSearch in Google Scholar
  • 25 Takeda Y, Takeda A. Plasma levels of t-PA, free PAI-1 and a complex with t-PA with PAI-1 in human males and females at various ages. Thromb Res 1989; 55: 601-9
    CrossrefPubMedSearch in Google Scholar
  • 26 Fishman ML, Langleben D, Moroz LA. Fibrinolytic response to venous occlusion. Comparison of radiofibrin solid phase assay and euglobulin lysis, with observations on cellular composition of blood. Progr Chem Fibrinol Thrombol 1983; 6: 436-9
    PubMedSearch in Google Scholar
  • 27 Grau E, Moroz LA. Fibrinolytic activity of normal human blood monocytes. Thromb Res 1989; 52: 145-62
    PubMedSearch in Google Scholar
  • 28 Langleben D, Moroz LA. Participation of blood cells in exercise-induced fibrinolysis. Thromb Res 1985; 39: 733-40
    CrossrefPubMedSearch in Google Scholar
  • 29 Danø K, Andreasen PA, Grandahl-Hansen J, Kristensen P, Nielsen LS, Skriver L. Plasminogen activators, tissue degradation and cancer. Adv Cancer Res 1985; 44: 139-266
    PubMedSearch in Google Scholar