PAI-1 activity

Hansen, J., Grimsgaard, S., Nordoy, A. and Bonaa, K.H. (2000) Dietary supplementation with highly purified eicosapentaenoic acid and docosahexaenoic acid does not influence PAI-1 activity. Thromb. Res. 98 123-132. 

Rosen, S., Wejkum, L., Billing-Claeson, S., et al.. Evaluation of a bioimmunoassay for t-PA activity and its relation to PAI-1 activity and antigen levels. Fibrinol. Proteol. 12, 340-346 (1999). 

Devaraj S, Jialal I, Rockwood J, Zak D (2011) Effect of orange juice and beverage with phytosterols on cytokines and PAI-1 activity. Clin Nutr 30(5) 668-671. doi 10.1016/J. clnu.2011.03.009... 

Little is known about the relative effects on fibrinolytic capacity of saturated fatty acids compared with unsaturated fatty acids. It has been reported, however, that diets rich in butterfat decreased PAI-1 activity compared with a diet rich in partially hydrogenated soybean oil, but whether this is because of changes in the saturated acid or the trans fatty acid content is not clear from this study. 

Fibrinolysis Increased PAI-1 activity of a palmitic acid-rich diet has been observed compared with diets enriched with oleic acid, indicating impaired fibrinolytic capacity of the plasma. However, this was not confirmed by other experiments on the effects of particular saturated fatty acids (including palmitic acid), which did not indicate changes in fibrinolytic capacity of the blood, measured as tPA, PAI-1 activity, or antigen concentrations of tPA and PAI-1. 

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. 

Inhibits platelet aggregation by increasing levels of cAMP Binds protein C, which is then cleaved by thrombin to yield activated protein C this in combination with protein S degrades factors Va and Villa, limiting their actions Activates plasminogen to plas-min, which digests fibrin the action of t-PA is opposed by plasminogen activator inhibitor- (PAI-1)... 

BMI body mass index PAI-1 plasminogen activator inhibitor-1... 

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. 

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). 

Levin E. G., Santell L. Association of a plasminogen activator inhibitor (PAI-1) with the growth substratum and membrane of human endothelial cells. J Cell Biol 1987 105, 2543-9. 

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. 

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). 

J2. Janicke, F., Schmitt, M., Pache, L., Ulm, K., Harbeck, N., Hoffer, H., and Graeff, H., Urokinase plasminogen activator (uPA) and its inhibitor PAI-1 are strong and independent prognostic factors in node-negative breast cancer. Breast Cancer Res. Treat. 24, 195-208 (1993). 

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

TG, triglyceride HDL, high-density lipoprotein LDL, low-density lipoprotein PAI-1, plasminogen activator inhibitor-1. Note not all of these features will be present in every insulin-resistant individual. 

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. 

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