Plasminogen activator inhibitor 1 PAI

A number of adipokines are linked to inflammation and immunity (Fig. 1). This includes both leptin and adiponectin, and also a number of other key inflammatory proteins, particularly cytokines and chemokines [1]. The cytokines and chemokines encompass interleukin-1(3 (EL-1 (3), IL-6, DL-10, TNFa, monocyte chemoattractant protein-1 (MCP-1), and macrophage migration inhibitory factor (MIF). Other major inflammation-related adipokines include nerve growth factor (NGF), and acute phase proteins such as serum amyloid A and haptoglobin. In addition, adipocytes secrete plasminogen activator inhibitor-1 (PAI-1), which is an important thrombotic factor as well as an acute phase protein. 

The measurement of plasminogen activator inhibitor-1 (PAI-1), which complexes with tissue plasminogen activator (t-PA) and thus affects the ability of the latter to activate fibrinolysis, is useful in the assessment of fibrinolytic disorders (93). The complex formed by the fibrinolytic enzyme plasmin with its inhibitor... 

Some physiological variables influence the measurement of fibrinolytic activators and inhibitors. For instance, both t-PA and plasminogen activator inhibitor 1 (PAI-1) levels in plasma are subject to diurnal variation in a 12-hour period. Even in samples taken at the same time of day the coefficient of variation (CV) of measured PAI levels range from 8 to 143% To account for this diurnal variation, blood samples spaced over several time intervals during a 24-hour period should be collected. Consumption of alcohol induces the PAI level in plasma. The half-life of t-PA is 360 seconds. However, in the presence of trauma or inflammation, when the PAI-1 level is expected to be elevated 10-fold, the half-life of t-PA is reduced to 36 seconds (114). 

Wygrecka, M., Morty, R.E., Markart, P., Kanse, S.M., Andreasen, P.A., Wind, T., Guenther, A., and Klaus, T.P. (2007) Plasminogen activator inhibitor-1 (PAI-1) is an inhibitor of factor VILactivating protease in patients with acute respiratory distress syndrome. J. Biol. Chem., 10.1074/jbc.M610748200, published online ahead of print. 

Plasminogen activator inhibitor-1 (PAI-1) Systemic Haemostatic system Inhibits fibrinolysis... 

Protein C exerts an antithrombotic effect by inhibiting Factors Va and Villa. In vitro data indicate that it has indirect prohbri-nolytic activity through its abhity to inhibit plasminogen activator inhibitor-1 (PAI-1) and to hmit production of activated throm-bin-activatable-hbrinolysis inhibitor. In vitro data also indicate that Activated Protein C may exert an anti-inflammatory effect by inhibiting human tumor necrosis factor production by monocytes, by blocking leukocyte adhesion to selectins, and by hmiting thrombin-induced inflammatory responses within the microvascular endothehum. 

The effect of continuously administered low-dose 17-beta-estradiol (E2) + norethisterone acetate (NETA) on coagulation and fibrinolytic factors has been studied in 120 menopausal women, using two dosage variations (1 mg of E2 with 0.25 mg or 0.5 mg of NETA) compared with placebo over a year (53). In either dose, the combination significantly lowered plasma concentrations of factor VII, fibrinogen, antithrombin, and plasminogen activator inhibitor-1 (PAI-1) compared with placebo. These changes appear favorable, since they may lead to increased fibrinolytic activity and could reduce the risk of coronary heart disease. However, antithrombin activity was also reduced, which may increase the risk of venous thromboembolism. 

Pinsky DJ, Liao H, Lawson CA et al. (1998) Coordinated induction of plasminogen activator inhibitor-1 (PAI-1) and inhibition of plasminogen activator gene expression by hypoxia promotes pulmonary vascular fibrin deposition. J Clin Invest 102 919-928... 

The sensitivity of many serine-protease inhibitors (serpins) to ROIs has been determined in a number of groups and is summarized in Table 2. Of these serine-protease inhibitors, the most sensitive to inactivation by oxidants like OC1- or chloramines are those which contain methionine at or juxtaposed to the reactive centre [49] (e.g. plasminogen activator-inhibitor-1 (PAI-1), oq-proteinase inhibitor and 0(2-antiplasmin). Inactivation is thought to principally be due to the oxidation of these methionine residues to methionine sulfoxide [50-52]. PAI-1, which is rapidly inactivated in plasma, is also extremely sensitive to oxidants like iV-chlorosuccinimide, chloramine-T and H2O2, through a reaction involving oxidation of the reactive-site methionine. 

ECM migration tracks. The assay is based on the immunohisto-chemical detection of ECM components deposited on the substratum by the cells while migrating (Bade and Nitzgen, 1985 Bade and Feindler, 1988). Laminin (Bade and Nitzgen, 1985), fibronectin (Bade and Feindler, 1988 Seebacher et al., 1988), plasminogen activator inhibitor-1 (PAI-1 Seebacher et al., 1992) have been used as ECM track markers. 

The effect of nicotine, the main principle of tobacco, on PKC activity was measured as a function of time. At a concentration of 100 nmol/1, nicotine caused an increase in PKC activity in endothelial cells from human adult CNS. The increase in PKC activity was significant in 30 s and attained maximum levels at 2 min. In order to assess the significance of the nicotine-induced PKC activation in the observed increase in plasminogen activator inhibitor-1 (PAI-1) production, the effect of nicotine was measured in the presence of the PKC inhibitor GF-109203-X. In these conditions, nicotine had no effect on PAI-1 mRNA levels. Similar results were obtained with another PKC inhibitor (calphostin C), demonstrating that in CNS-endothelial cells PAI-1 mRNA expression and protein production are dependent on the activation of PKC [31]. 

Corticosteroids have antiangiogenic, antifibrotic, and antipermeability properties. The principle effects of steroids are stabilization of the blood-retinal barrier, resorption of exudation, and downregulation of inflammatory stimuli. Antiangiogenesis is a secondary effect felt to be mediated primarily by upregulation of extracellular matrix protein plasminogen activator inhibitor-1 (PAI-1) in vascular endothelial cells (18). This inhibits activation of plasmin and alters extracellular matrix degradation. 

H Pannekoek, M van Meijer, RR Schleef, DJ Loskutoff, CD Barbas. Functional display of human plasminogen-activator inhibitor 1 (PAI-1) on phages novel perspectives for structure-function analysis by error-prone DNA synthesis. Gene 128 135-140, 1993. 

D5. Declerck, P. J., Moreau, H., Jespersen, J., Gram, J., and Kluft, C., Multicenter evaluation of commercially available methods for the immunologic determination of plasminogen activator inhibitor-1 (PAI-1). Thromb. Haemost. 70, 858-863 (1993). 

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