Plasminogen activator inhibitor type

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). 

Additionally, attention has been focused on some factors that, operating in the hemostatic balance, have been attributed the role of risk markers of clinical events. Thus, increased plasma concentration of factor VII, fibrinogen, plasminogen activator inhibitor type 1 (PAI-1), and the already mentioned Lp(a) have been associated with the occurrence of CHD. Much work has been done on the modulation of these factors by HT (for a review see Cano and Van Baal 2001), and both similarities and differences have been found in the sparse literature on SERM action. Raloxifene and droloxifene decrease fibrinogen more actively than does HT (Walsh et al. 1998 Herrington et al. 2000). In contrast, the effective reduction demonstrated for PAI-1 with oral HT was not confirmed for raloxifene or droloxifene (Walsh et al. 1998 de Valk-de Roo et al. 1999 Herrington et al. 2000). 

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). 

KI5. Kristensen, P., Pyke, C., Lund, L. R., Andreasen, P. A., and Dano, K., Plasminogen activator inhibitor type-1 in Lewis lung carcinoma. Histochemistry 93, 559-566 (1990). 

Fibrinolysis is also inhibited by plasminogen activator inhibitor type 1, which is a 50 kDa serine protease inhibitor released from platelets and endothelial cells in response to various stimuli. Plasminogen activator inhibitor-1 binds to fibrin via high- or low-affinity sites and can inhibit t-PA also bound to the clot (Keijer et al., 1991 Stringer and Pannekoek, 1995). This is an important pathway for limiting fibrinolysis, especially in platelet-rich thrombi and regions near endothelial cells. 

Tierney, M.J. and Medcalf, R.L. (2001) Plasminogen Activator Inhibitor Type 2 Contains mRNA Instability Elements within Exon 4 of the Coding Region. J. Biol. Chem., 276, 13675-13684. 

Reilly TM, Mousa SA, Seetharam R, Racanelli AL. Recombinant plasminogen activator inhibitor type I a review of structural, functional, and biological aspects. Blood Coag Fibrinol 1994 5(l) 78 83. 

PLAT Plasminogen activator, tissue serine (or cysteine) proteinase inhibitor, Clade E (nexin, plasminogen activator inhibitor type 1), member 1... 

Olson D, Pollanen J, Hoyer-Hansen G, Ronne E, Sakaguchi K, Wun TC, et al. Internalization of the urokinase-plasminogen activator inhibitor type-1 complex is mediated by the urokinase receptor. J Biol Chem 1992 267(13) 9129-9133. 

Mcllroy M, O Rourke M, McKeown SR, Hirst DG, Robson T. Pericytes influence endothelial cell growth characteristics Role of plasminogen activator inhibitor type 1 (PAI-1). Cardiovasc Res 2006 69 207-217. 

Duymelinck C, Dauwe SE, Nouwen EJ, De Broe ME, Verpooten GA. Cholesterol feeding accentuates the cyclosporine-induced elevation of renal plasminogen activator inhibitor type 1. Kidney Int 1997 51 1818-1830. 

Janicke F, Prechtl A, Thomssen C. Randomized adjuvant chemotherapy trial in high-risk, lymph nodenegative breast cancer patients identified by urokinase-type plasminogen activator and plasminogen activator inhibitor type 1. J Natl Cancer Inst 2001 93 913-20. 

Huber K, Christ G, Wojta J, Gulba D. Plasminogen activator inhibitor type-1 in cardiovascular disease. Status report 2001. Thromb Res 2001 103 Suppl lS7-19. 

H P. Kohler and P. J. Grant Plasminogen-activator inhibitor type 1 and coronary artery disease. New England Journal of Medicine 342, 1792 (2000). 

PAI-1 plasminogen-activator inhibitor type 1 PCC prothrombin complex concentrate PT prothrombin time vWF Ag von Willebrand factor antigen... 

Harbeck N, Kates RE, Look MR et al. Enhanced benefit from adjuvant chemotherapy in breast cancer patients classified high-risk according to urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor type 1 (n=3424). Cancer Res 2002 62 4617 622. 

Falk K, et al. (2001). Reduction of experimental adhesion formation by inhibition of plasminogen activator inhibitor type 1. Br. J. Surg. 88 286-289. 

Yu H, Stasinopoulos S, Leedman P, et al. (2003). Inherent instability of plasminogen activator inhibitor type 2mRNAis regulated by tristetraprolin.7. Biol. Chem. 218 13912-13918. 

Fig. 15.3 Pathogenesis of acute vascular rejection. Activation of endothelium by xenoreactive antibodies (Ab), complement (C), platelets, and perhaps by inflammatory cells (natural killer (NK) cells and macrophages (M0) leads to the expression of new pathophysiologic properties. These new properties, such as the synthesis of tissue factor (TF) and plasminogen activator inhibitor type 1 (PAI-1), promote coagulation the synthesis of -selectin and cytokines such as ILIa promote inflammation. These changes in turn cause thrombosis, ischemia, and endothelial injury, the hallmarks of acute vascular rejection. (Adapted from Nature 1998 392(Suppl.) 11-17, with permission.)...

Cl. Castello, R., Estelles, A., Vazquez, C., et al.. Quantitative real-time reverse transcription-PCR assay for urokinase plasminogen activator, plasminogen activator inhibitor type 1, and tissue metalloproteinase inhibitor type 1 gene expressions in primary breast cancer. Clin. Chem. 48, 1288-1295 (2002). 

V., Plasminogen- and colony-stimulating factor-1 associated markers in bladder carcinoma Diagnostic value of urokinase plasminogen activator receptor and plasminogen activator inhibitor type-2 using immunocytochemical analysis. Urol. Res. 30, 301-309 (2002). 

H7. Huang, Y., Haraguchi, M., Lawrence, D. A., Border, W. A., u, L., and Noble, N. A., A mutant, noninhibitory plasminogen activator inhibitor type 1 decreases matrix accumulation in experimental glomerulonephritis. J. Clin. Invest. 112, 379-388 (2003). 

LIO. Liu, K., Feng, Q., Gao, H. J., et al.. Expression and regulation of plasminogen activators, plasminogen activator inhibitor type-1, and steroidogenic acute regulatory protein in rhesus monkey corpus luteum. Endocrinology 144, 3611-3617 (2003). 

N2. Nicholls, S. C., Hoffer, E. K., and Chandler, W. L., Failure of peripheral arterial thrombolysis due to elevated plasminogen activator inhibitor type 1. Blood Coagul. Fibrinolysis. 14, 729-733 (2003). 

Nordt, T.K., Klassen, K.J., Schneider, D.J., and Sobel, B.E. (1993) Augmentation of synthesis of plasminogen activator inhibitor type-1 in arterial endothelial cells by glucose tmd its implications for local fibrinolysis. Arterioscler. Thromb., 13 1822-1828. 

Pandolfi, A., Giaccari, A., CM, C., Alberta, M.M., Morviducd, L., De Filippis, E.A., Buongiomo, A., Pellegrini, G., Capani, F., and Consoli, A. (2001) Acute hypeiglycemia and acute hyperin-sulinemia decrease plasma fibrinolytic activity and increase plasminogen activator inhibitor type 1 in the rat. Acta DiabetoL, 38 71-76. 

Medcalf RL, Stasinopoulos SJ. The undecided serpin the ins and outs of plasminogen activator inhibitor Type 2. FEBS J 2005 2724858-4867. 

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