U-plasminogen activator

Fig. 3. Overview of puriftcation sequence for the nonrecombinant tissue plasminogen activator (t-PA) which also contains urokinase plasminogen activator (u-PA). Serum-free culture conditional media is from normal human ceU line. The temperature for aU. steps, except for size-exclusion chromatography...

Zivin JA, Fisher M, DeGirolami U, Hemenway CC, Stashak JA. Tissue plasminogen activator reduces neurological damage after cerebral embolism. Science. 1985 230 1289-1292. 

Zivin JA, Lyden PD, DeGirolami U, Kochhar A, Mazzarella V, Hemenway CC, Johnston P. Tissue plasminogen activator. Reduction of neurologic damage after experimental embolic stroke. Arch Neurol. 1988 45 387-391. 

Straub S, Junghans U, Jovanovic V, Wittsack HJ, Seitz RJ, Siebler M. Systemic thrombolysis with recombinant tissue plasminogen activator and tirofiban in acute middle cerebral artery occlusion. Stroke 2004 35 705-709. 

The procoagulant factors produced by endothelial cells are the coagulation factors von Willebrand factor (WF), F-V, F-VIII, tissue factor (TF), and plasminogen activator inhibitor (PAI), which blocks the activators u-PA and t-PA and counteracts fibrinolysis (G21, FI6). It has been shown that under the influence of complement activation (C9), in response to endotoxin in vitro (C24), in experimental E. coli sepsis in baboons (D30), and after stimulation with TNF (Al, N6), endothelial cells up-regulate the expression of TF, down-regulate TM and inhibit the production of t-PA and PAF. Thus, the balance may shift in the procoagulant direction with a large excess of PAI-1. 

Plasminogen activator inhibitor type 2 (PAI-2) is present in human placenta and monocytes (37, 42). The single-chain inhibitor molecule (sPAI-2) inhibits both two-chain u-PA and two-chain t-PA. Its inhibition is 10 times greater for two-chain u-PA compared with two-chain t-PA and it inhibits single-chain t-PA only minimally (37). Plasma concentrations of PAI-2 up to 2 p,M have been observed in the third trimester of pregnancy (42). 

C2. Cajot, J. F., Bamat, J., Bergonzelli, G. E., Kruithof, E., Medcalf, R. L., Tetuz, J., and Sordat, B., Plasminogen activator inhibitor type lisa potent natural inhibitor of extracellular matrix degradation by fibrosarcoma and colon carcinoma cells. Proc. Natl. Acad. Sci. U.S.A. 50, 4676-4684 (1990). 

Pharmaceutical preparations containing plasminogen activators. Boehringer Mannheim Gmbh, Mannheim, Germany. U.S. Patent No. 5747030, issued 8-21-96. 

Olofsson, B., Korpelainen, E., Pepper, M.S., Mandriota, S.J., Aase, K., Kumar, V., Gunji, Y., Jeltsch, M.M., Shibuya, M., Alitalo, K. and Eriksson, U. (1998) Vascular endothelial growth factor B (VEGF-B) binds to VEGF receptor-1 and regulates plasminogen activator activity in endothelial cells. Proc. Natl Acad. Sci. USA, 95, 11709-11714. 

Hajjar, K.A., Mauri, L., Jacovina, A.T., Zhong, F., Mirza, U.A., Padovan, J.C., and B.T. Chait, 1998, Tissue plasminogen activator binding to the annexin II tail domain. Direct modulation by homocysteine. J. Biol. Chem. 273, 9987-9993. 

Brener SJ, Zeymer U, Adgey AA, Vrobel TR, Eptifibatide and low-dose tissue plasminogen activator in acute myocardial infarction. The integrilin and low-dose thrombolysis in acute myocardial infarction (INTRO AMI) trial, J Am Coll Cardiol 2002 39 377. 

Zeymer U, von Essen R, Tebbe U, et al, Frequency of optimal anticoagulation for acute myocardial infarction after thrombolysis with front-loaded recombinant tissue-type plasminogen activator and conjunctive therapy with recombinant hirudin (HBW 023). ALKK Study Group. Am J Cardiol 1995 76 997-1001. 

Harbeck N, Alt U, Berger U et al (2001) Prognostic impact of proteolytic factors (urokinase-type plasminogen activator, plasminogen activator inhibitor 1, and cathepsins B, D, and L) in primary breast cancer reflects effects of adjuvant systemic therapy. Clin Cancer Res 7 2757-2764... 

Ploug M, Kjalke M, Ronne E, Weidle U, Hoyer-Hansen G, Dano K. Localization of the disulfide bonds in the NH2-terminal domain of the cellular receptor for human urokinase-type plasminogen activator. A domain structure belonging to a novel superfamily of glycolipid-anchored membrane proteins. J Biol Chem 1993 268(23) 17539-17546. 

Ronne E, Behrendt N, Ploug M, Nielsen HJ, Wollisch E, Weidle U, et al. Quantitation of the receptor for urokinase plasminogen activator by enzyme-linked immunosorbent assay. J Immunol Methods 1994 167(1-2) 91-101. 

Given that knock-outs of prothrombotic factors yield mice with bleeding tendencies, it follows that deletion of factors in the fibrinolytic pathway results in increased thrombotic susceptibility in mice. Plasminogen (Bugge et al. 1995 Ploplis et al. 1995), tissue plasminogen activator (t-PA), urokinase-type plasminogen activator (u-PA), and the combined t-PA/u-PA knock-out (Carmeliet et al. 1994) result in mice that... 

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