RSS-Feed abonnieren
DOI: 10.1055/s-0038-1647459
Physical Exercise Induces Enhancement of Urokinase-Type Plasminogen Activator (u-PA) Levels in Plasma
Publikationsverlauf
Received 28. Juni 1990
Accepted after revision 28. August 1990
Publikationsdatum:
02. Juli 2018 (online)
![](https://www.thieme-connect.de/media/10.1055-s-00035024/199101/lookinside/thumbnails/10-1055-s-0038-1647459-1.jpg)
Summary
The enhancement of the blood fibrinolytic potential by physical exercise is generally attributed to the release of tissue-type plasminogen activator (t-PA) from the vessel wall. In this study we have investigated the possible contribution of urokinase-type plasminogen activator (u-PA).
Six healthy male volunteers (age 21–25 years) were screened for their ability to perform maximal exercise for their age-group for 12 min on a bicycle ergometer. Subsequently, on one occasion they were required to remain supine for 2 h (from 8.30 a. m. onwards) and on another they performed maximal exercise (from 9.00 a.m. onwards). During exercise an increase in u-PA antigen and plasmin-activatable pro-urokinase (proUK) activity, concurrent with t-PA antigen and euglobulin t-PA activity, was observed in all six volunteers, while at rest these parameters remained unaffected. Mean u-PA- and t-PA antigen increased, respectively, from 4.2 ± 1.0 ng/ml and 5.8 ± 2.1 ng/ml before exercise to 9.8 ± 3.0 ng/ml and 18.3 ± 3.8 ng/ml (peak). Mean plasminactivatable proUK activity and t-PA activity increased, respectively, from 2.1 ± 0.4 ng/ml and 0.3 ± 0.2 ng/ml before exercise to 4.3 ± 1.7 ng/ml and 7.2 ± 4.0 ng/ml (peak). The increases were statistically significant throughout (paired t-test, pre vs post, antigen P <0.005 and activity P <0.02). After cessation of exercise u-PA and t-PA declined concurrently to normal values with a 50"/" decay in about 5 min. In conclusion, we found that both u-PA antigen and plasmin-activatable proUK activity are, concurrently with t-PA, enhanced upon exercise and, therefore, we consider that u-PA also contributes to – and co-operates in – the enhancement of the blood fibrinolytic potential and activity under these conditions.
-
References
- 1 Biggs R, MacFarlane RG, Pilling J. Observations on fibrinolysis. Experimental activity produced by exercise or adrenaline. Lancet 1947; 1: 402-405
- 2 Sherry S, Lindemeyer RI, Fletcher AP, Alkjaersig N. Studies on enhanced fibrinolytic activity in man. J Clin Invest 1959; 38: 810-822
- 3 Iatridis SG, Ferguson JH. Effect of physical exercise on blood clotting and fibrinolysis. J Appl Physiol 1963; 18: 337-344
- 4 Bennett B, Ogston CM, Ogston D. The effect of prolonged exercise on the components of the blood fibrinolytic system. J Physiol 1968; 198: 479-485
- 5 Nilsson IM, Pandolfi M, Robertson B. Properties of fibrinolytic activators appearing after venous stasis and intravenous injection of nicotinic acid. Coagulation 1970; 3: 13-21
- 6 Rosing DR, Brakman P, Redwood DR, Goldstein RE, Beiser GD, Astrup T, Epstein SE. Blood fibrinolytic activity in man: diurnal variation and response to varying intensities of exercise. Circ Res 1970; 27: 171-184
- 7 Astrup T. The effects of physical activity on blood coagulation and fibrinolysis. In: Naughton JP, Hellerstein K. (eds). Exercise Testing and Exercise Training in Coronary Heart Disease. Academic; New York: 1973: 169-192
- 8 Cash JD, Gader AM A, De Costa J. Release of plasminogen activator and factor VIII to lysine vasopressin, arginine vasopressin, 1-Desamino-8-d-vasopressin, angiotensin and oxytocin in man. Br J Haematol 1974; 27: 363-364
- 9 Mannuci PM, Aberg M, Nilsson IM, Robertson B. Mechanism of plasminogen activator and factor VIII increase after vasoactive drugs. Br J Haematol 1975; 30: 81-93
- 10 Kluft C. Studies on the fibrinolytic system in human plasma: Quantitative determination of plasminogen activators and proactivators. Thromb Haemostas 1979; 41: 365-383
- 11 Rijken DC, Wijngaards G, Welbergen J. Relationship between uterine tissue plasminogen activator and the activators in blood and vascular wall. Thromb Res 1980; 18: 815-830
- 12 Marsh NA, Gaffney PJ. Some observations on the release of extrinsic and intrinsic plasminogen activators during exercise in man. Haemostasis 1980; 9: 238-247
- 13 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: 279-288
- 14 Rijken DC, Juhan-Vague I, De Cock F, Collen D. Measurement of human tissue-type plasminogen activator by a two-site immunoradiometric assay. J Lab Clin Med 1983; 101: 274-284
- 15 Kluft C, Jie AF H, Allen RA. Behaviour and quantitation of extrinsic (tissue-type) plasminogen activator in blood. Thromb Haemostas 1983; 50: 518-520
- 16 Prowse CV, Farrugia A, Boulton FE, Tucker J, Ludlam CA, McLaren M, Belch JJ F, Prentice CR M, Dawes J, MacGregor IR. A comparative study using immunological and biological assays of the haemostatic responses to DDAVP infusion, venous occlusion and exercise in normal men. Thromb Haemostas 1984; 51: 110-114
- 17 Prowse CV, MacGregor IR. Regulation of the plasminogen activator level in blood. In: Kluft C. (ed). Tissue-type plasminogen activator (t-PA): Physiological and clinical aspects. CRC Press; Boca Raton, FL: 1988. II 49-66
- 18 Lowe GD O, Small M. Stimulation of endogenous fibrinolysis. In: Kluft C. (ed). Tissue-type Plasminogen Activator (t-PA): Physiological and Clinical Aspects. CRC Press; Boca Raton, FL: 1988. II 129-169
- 19 Kluft C, Trumpi-Kalshoven MM, Jie AF H, Veldhuyzen-Stolk EC. Factor XH-dependent fibrinolysis: a double function of plasma kallikrein and the occurence of a previously undescribed factor XII-and kallikrein-dependent plasminogen proactivator. Thromb Haemostas 1979; 41: 756-773
- 20 Wijngaards G, Kluft C, Groeneveld E. Demonstration of urokinase-related fibrinolytic activity in human plasma. Br J Haematol 1982; 51: 165-169
- 21 Wun TC, Schleuning WD, Reich E. Isolation and characterization of urokinase from human plasma. J Biol Chem 1982; 257: 3276-3283
- 22 Tissot JD, Schneider P, Hauert J, Ruegg M, Kruithof EK O, Bachmann F. Isolation from human plasma of a plasminogen activator identical to urinary high molecular weight urokinase. J Clin Invest 1982; 70: 1320-1323
- 23 Lijnen HR, Collen D. Interaction of plasminogen activators and inhibitors with plasminogen and fibrin. Semin Thromb Hemostas 1982; 8: 2-10
- 24 Kluft C, Dooijewaard G, Emeis JJ. Role of the contact system in fibrinolysis. Semin Thromb Hemostas 1987; 13: 50-68
- 25 Bachmann F. Fibrinolysis. In: Verstraete M, Vermijlen J, Lijnen HR, Arnout J. (eds). Thrombosis and Haemostasis. International Society on Thrombosis and Haemostasis and Leuven University Press; Leuven: 1987: 227-263
- 26 Brommer EJ P, Schicht I, Wijngaards G, Verheijen JH, Rijken DC. Fibrinolytic activators and inhibitors in terminal renal insufficiency and in anephric patients. Thromb Haemostas 1984; 52: 311-314
- 27 Huisveld IA, Kluft C, Hospers AJ H, Bernink MJ E, Erich WB M, Bouma BN. Effect of exercise and oral contraceptive agents on fibrinolytic potential in trained females. J Appl Physiol: Respirat Environ Exercise Physiol 1984; 56: 906-913
- 28 Darras V, Thienpont M, Stump DC, Collen D. Measurement of urokinase-type plasminogen activator (u-PA) with an enzyme-linked immunosorbent assay (ELISA) based on three murine monoclonal antibodies. Thromb Haemostas 1986; 56: 411-414
- 29 Levi M, ten Cate JW, Dooijewaard G, Sturk A, Brommer EJ P, Agnelli G. DDAVP induces systemic release of urokinase-type plasminogen activator. Thromb Haemostas 1989; 62: 686-689
- 30 Fortuin NJ. Exercise stress testing. Circulation 1977; 56: 699-712
- 31 Verheijen JH, Mullaart E, Chang GT G, Kluft C, Wijngaards G. A simple, sensitive spectrophotometric assay for extrinsic (tissue-type) plasminogen activator applicable to measurements in plasma. Thromb Haemostas 1982; 48: 266-269
- 32 Gaffney PJ, Curtis AD. A collaborative study of a proposed international standard for tissue-type plasminogen activator (t-PA). Thromb Haemostas 1985; 53: 134-136
- 33 Binnema DJ, van Iersel JJ L, Dooijewaard G. Quantitation of urokinase antigen in plasma and culture media by use of an ELISA. Thromb Res 1986; 43: 569-577
- 34 Dooijewaard G, van Iersel JJ L, Brommer EJ P. Quantitation of proUK, UK and UK. Inhibitor levels in plasma of patients and healthy man. In: Binder BR. (ed). Abstracts of the Eighth International Congress on Fibrinolysis, Vienna 1986; Churchill Livingstone, Edinburgh: 1986: 142
- 35 Mahmoud M, Gaffney PJ. Bioimmunoassay (BIA) of tissue plasminogen activator (t-PA) and its specific inhibitor (t-PA/INH). Thromb Haemostas 1985; 53: 356-359
- 36 Booth NA, Walker E, Maughan R, Bennett B. Plasminogen activator in normal subjects after exercise and venous occlusion: t-PA circulates as complexes with C1-Inhibitor and PAI-1. Blood 1987; 69: 1600-1604
- 37 Hoylaerts M, Rijken DC, Lijnen HR, Collen D. Kinetics of the activation of plasminogen by human tissue plasminogen activator. Role of fibrin. J Biol Chem 1982; 257: 2912-2919
- 38 Collen D, Stassen JM, Stump DC, Verstraete M. Synergism of thrombolytic agents in vivo. Circulation 1986; 74: 838-842
- 39 Gurewich V, Pannell R. A comparative study of the efficacy and specificity of tissue plasminogen activator and pro-urokinase: Demonstration of synergism and of different thresholds of non-selectivity. Thromb Res 1986; 44: 217-228
- 40 Collen D, Stump DC, van de Werf F. Coronary thrombolysis in patients with acute myocardial infarction by intravenous infusion of synergic thrombolytic agents. Am Heart J 1986; 112: 1083-1084
- 41 Pannell R, Black J, Gurewich V. Complementary modes of action of tissue-type plasminogen activator and pro-urokinase by which their synergistic effect on clot lysis may be explained. J Clin Invest 1988; 81: 853-859
- 42 Gurewich V. Importance of fibrin specificity in therapeutic thrombolysis and the rationale of using sequential and synergistic combinations of tissue plasminogen activator and pro-urokinase. Semin Thromb Hemostas 1989; 15: 123-128
- 43 Bykowska K, Levin EG, Rijken DC, Loskutoff DJ, Collen D. Characterization of a plasminogen activator secreted by cultured bovine aortic endothelial cells. Biochim Biophys Acta 1982; 703: 113-115
- 44 Booyse FM, Osikowicz G, Feder S, Scheinbuks J. Isolation and characterization of a urokinase-type plasminogen activator (Mr = 54,000) from cultured human endothelial cells indistinguishable from urinary urokinase. J Biol Chem 1984; 259: 7198-7205
- 45 van Hinsbergh VW M, Binnema D, Scheffer MA, Sprengers EW, Kooistra T, Rijken DC. Production of plasminogen activators and inhibitor by serially propagated endothelial cells from adult human blood vessels. Arteriosclerosis 1987; 7: 389-400
- 46 Wojta J, Hoover RL, Daniel TO. Vascular origin determines plasminogen activator expression in human endothelial cells. J Biol Chem 1989; 264: 2846-2852
- 47 van Hinsbergh VW M, van den Berg EA, Fiers W, Dooijewaard G. Tumor necrosis factor induces the production of urokinase-type plasminogen activator by human endothelial cells. Blood 1990; 75: 1991-1998
- 48 de Boer A, Kluft C, Kasper FJ, Kroon JM, Schoemaker HC, Breimer DD, Soons PA, Emeis JJ, Pruis J, Cohen AF. The clearance of recombinant human tissue-type plasminogen activator is dependent on liver blood flow. In: Kluft C, Verheijen JH. (eds). Abstracts of the Leiden Fibrinolysis Workshop 3 on Life Style & Fibrinolysis, Leiden 1990; Leiden: 1990: 67
- 49 Collen D, De Cock F, Lijnen HR. Biological and thrombolytic properties of proenzyme and active forms of human urokinase - II. Turnover of natural and recombinant urokinase in rabbits and squirrel monkeys. Thromb Haemostas 1984; 52: 24-26
- 50 Stump DC, Kieckens L, De Cock F, Collen D. Pharmacokinetics of single chain forms of urokinase-type plasminogen activator. J Pharm Exp Ther 1987; 242: 245-250