INT1925

Context Info Confidence 0.75 First Reported 1979 Last Reported 2010 Negated 0 Speculated 2 Reported most in Body Documents 47 Total Number 50 Disease Relevance 34.76 Pain Relevance 7.88

peptidase activity (PLAT) protein modification process (PLAT) extracellular space (PLAT) extracellular region (PLAT) cytoplasm (PLAT)

Anatomy Link Frequency plasma 12 plaque 4 extracellular matrix 3 forearm 1 MCF-7 1 PLAT (Homo sapiens)

Pain Link Frequency Relevance Heat Inflammation 402 99.98 cINOD 12 99.80 Migraine 152 99.04 alcohol 24 98.48 Angina 52 97.40 fibrosis 16 97.36 pain flank 1 97.28 depression 11 97.08 cva 161 96.96 bradykinin 54 96.96

Disease Link Frequency Relevance Heat Atherosclerosis 180 100.00 INFLAMMATION 520 99.98 Increased Venous Pressure Under Development 229 99.64 Diabetes Mellitus 822 99.30 Breast Cancer 60 99.12 Headache 150 99.04 Myocardial Infarction 297 99.00 Infarction 13 98.82 Hemorrhage 43 98.76 Coronary Artery Disease 245 98.62

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Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

Results of tPA-Ag and PAI-Ag are expressed in ng/ml.

Gene_expression (expressed) of tPA

1) Confidence 0.75 Published 2002 Journal BMC Cardiovasc Disord Section Body Doc Link PMC115848 Disease Relevance 0.05 Pain Relevance 0.04

Indeed, in patients treated > 6 hours after infarct in the GUSTO trial, streptokinase produced lower mortality results than accelerated recombinant tissue plasminogen activator (rt-PA).

Gene_expression (produced) of recombinant tissue plasminogen activator

2) Confidence 0.74 Published 1994 Journal Drugs Aging Section Abstract Doc Link 8130384 Disease Relevance 0.53 Pain Relevance 0.14

RESULTS: Following tissue injury, rofecoxib increased the expression of genes associated with degradation of the extracellular matrix, including MMP-1 (64.7 +/- 6.5, P = .010), MMP-3 (41.7 +/- 4.8, P = .007), PLAT (encoding tissue plasminogen activator) (10.9 +/- 4.6, P = .032), and IL8 (encoding interleukin 8) (8.3 +/- 6.7, P = .020), and decreased the expression of TIMP3 (encoding tissue inhibitor of metalloproteinase 3) (6.2 +/- 2.8, P = .027).

Gene_expression (expression) of tissue plasminogen activator in extracellular matrix

3) Confidence 0.69 Published 2006 Journal Clin. Pharmacol. Ther. Section Body Doc Link 16580899 Disease Relevance 0.14 Pain Relevance 0

RESULTS: Following tissue injury, rofecoxib increased the expression of genes associated with degradation of the extracellular matrix, including MMP-1 (64.7 +/- 6.5, P = .010), MMP-3 (41.7 +/- 4.8, P = .007), PLAT (encoding tissue plasminogen activator) (10.9 +/- 4.6, P = .032), and IL8 (encoding interleukin 8) (8.3 +/- 6.7, P = .020), and decreased the expression of TIMP3 (encoding tissue inhibitor of metalloproteinase 3) (6.2 +/- 2.8, P = .027).

Gene_expression (expression) of PLAT in extracellular matrix

4) Confidence 0.69 Published 2006 Journal Clin. Pharmacol. Ther. Section Body Doc Link 16580899 Disease Relevance 0.14 Pain Relevance 0

Reteplase was used in 120 patients and anistreplase/streptokinase in 130 patients.

Gene_expression (used) of Reteplase

5) Confidence 0.67 Published 2003 Journal Am. Heart J. Section Body Doc Link 12947366 Disease Relevance 0.08 Pain Relevance 0

Serum tissue polypeptide antigen (TPA) and plasma carcinoembryonic antigen (CEA) were simultaneously measured in 108 patients with breast cancer, in 40 healthy women, and in 26 women with benign breast disease.

Gene_expression (measured) of TPA in plasma associated with breast disease and breast cancer

6) Confidence 0.66 Published 1979 Journal J. Natl. Cancer Inst. Section Abstract Doc Link 292806 Disease Relevance 0.54 Pain Relevance 0

A variety of markers indicate endothelial dysfunction including: poor EC-dependent vasodilation, increased blood levels of von Willebrand factor (vWF), thrombomodulin, selectin, PAI-1, type IV collagen and t-PA were demonstrated in this patients population (Yaqoob et al 1993; Dosquet et al 1994; Myrup et al 1994; Makimattila et al 1996; Huszka et al 1997; Cosentino and Luscher 1998; Elhadd et al 1998; Malamitsi et al 1998; Huvers et al 1999).

Gene_expression (levels) of t-PA in blood associated with increased venous pressure under development

7) Confidence 0.65 Published 2007 Journal Vascular Health and Risk Management Section Body Doc Link PMC2350146 Disease Relevance 1.63 Pain Relevance 0

Inflammatory biomarkers (CRP, IL-6, fibrinogen), plasma viscosity, endothelial dysfunction markers (VWF, t-PA), and coagulation factors (VIII and IX, but not VII) were significantly higher in cases of MI/CHD death, but not in cases of incident angina compared with those who were CHD event free.

Gene_expression (biomarkers) of t-PA in plasma associated with coronary artery disease, inflammation, cva, death and myocardial infarction

8) Confidence 0.65 Published 2009 Journal Journal of Thrombosis and Haemostasis Section Body Doc Link PMC2810437 Disease Relevance 3.48 Pain Relevance 0.43

To exclude age dependent or pain related influences, age-matched patients with stable angina pectoris (NHYA II) and angiographically proven coronary artery disease (CAD, n = 16) or without evidence for coronary sclerosis (variant angina, n = 10; angina-like syndrome with normal coronary angiogram, n = 5; non-CAD, n = 15) have been investigated for their plasma PAI-1 activity and t-PA antigen levels.

Gene_expression (levels) of t-PA in coronary artery associated with stable angina pectoris, pain, angina, coronary artery disease and syndrome

9) Confidence 0.65 Published 1990 Journal Thromb. Haemost. Section Abstract Doc Link 2119522 Disease Relevance 1.75 Pain Relevance 0.54

g/100 g intravenous infusion); the sixth group (tEF, n = 6) was treated with t-PA plus eptifibatide (50 ?

Gene_expression (treated) of t-PA

10) Confidence 0.63 Published 2002 Journal BMC Cardiovasc Disord Section Body Doc Link PMC117121 Disease Relevance 0.17 Pain Relevance 0.10

Plasma levels of t-PA antigen and D-dimer were measured with enzyme-linked immunosorbent assays (ELISA) (Biopool AB, Umea, Sweden) as was VWF antigen (Dako, High Wycombe, UK).

Gene_expression (levels) of t-PA in Plasma

11) Confidence 0.58 Published 2009 Journal Journal of Thrombosis and Haemostasis Section Body Doc Link PMC2810437 Disease Relevance 0.63 Pain Relevance 0.06

BM 06.022 consists of the kringle 2 and protease domains of human tissue PA (tPA) and lacks oligosaccharide side chains because of its expression in Escherichia coli.

Gene_expression (expression) of tissue PA

12) Confidence 0.57 Published 1991 Journal J. Cardiovasc. Pharmacol. Section Abstract Doc Link 1719279 Disease Relevance 0.51 Pain Relevance 0

Increased circulating levels of vWF, PAI-1, t-PA, TFPI, and s-TM have been reported in patients with NIDDM (Collier et al 1992; McGill et al 1994; Bagg et al 2001; Aso et al 2002; Leurs et al 2002; Rigla et al 2006).

Gene_expression (levels) of t-PA associated with diabetes mellitus

13) Confidence 0.56 Published 2008 Journal Vascular Health and Risk Management Section Body Doc Link PMC2663449 Disease Relevance 1.20 Pain Relevance 0.04

In the I/R and tPA groups a significant increase in permeability was observed in postcapillary and collecting venules during reperfusion (baseline: 0.09 ± 0.01 normalized grey levels, p < 0.05, Fig. 3).

Gene_expression (groups) of tPA in venules

14) Confidence 0.55 Published 2002 Journal BMC Cardiovasc Disord Section Body Doc Link PMC117121 Disease Relevance 0.15 Pain Relevance 0.05

We used six groups: the control (I/R) (n = 5) group received an intravenous infusion of saline; the second group (tPA, n = 5) was treated with t-PA (human rtPA, Sigma Chemical, St.

Gene_expression (group) of tPA

15) Confidence 0.55 Published 2002 Journal BMC Cardiovasc Disord Section Body Doc Link PMC117121 Disease Relevance 0.20 Pain Relevance 0.10

Although the functional relevance of tPA variants are unknown, over expression of tPA leads to plasmin production, MMP activation and ECM degradation that is commonly associated with fetal membrane rupture and cervical ripening associated with PTB.

Gene_expression (expression) of tPA associated with rupture

16) Confidence 0.54 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2553267 Disease Relevance 0.30 Pain Relevance 0.07

Subsequently, in the Global Utilization of Streptokinase and Tissue plasminogen activator for Occluded coronary arteries (GUSTO-I) enzyme substudy [38], a 12% decrease in infarct size (as measured by ?

Gene_expression (activator) of Tissue plasminogen

17) Confidence 0.54 Published 2005 Journal Curr Control Trials Cardiovasc Med Section Body Doc Link PMC1236947 Disease Relevance 0.55 Pain Relevance 0.05

To the best of our knowledge no other studies have associated tPA markers with PTB; however, several studies have observed increased tPA and tissue factors expression in preterm compared to term human decidual tissues [34], [35]. tPA is a serine protease inhibitor in the fibrynolitic cascade (Figure 2) that converts inactive plasminogen to plasmin.

Gene_expression (expression) of tPA

18) Confidence 0.47 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2553267 Disease Relevance 0.31 Pain Relevance 0.09

PAI-1 represent the most important physiological inhibitor of tissue-type plasminogen activator (TPA) in plasma and elevated levels have been implicated in the pathogenesis of thromboembolic disease (Ridker 1992).

Gene_expression (represent) of TPA in plasma associated with cva

19) Confidence 0.46 Published 2008 Journal Vascular Health and Risk Management Section Body Doc Link PMC2663435 Disease Relevance 0.48 Pain Relevance 0.13

PAI-1 represent the most important physiological inhibitor of tissue-type plasminogen activator (TPA) in plasma and elevated levels have been implicated in the pathogenesis of thromboembolic disease (Ridker 1992).

Gene_expression (represent) of tissue-type plasminogen activator in plasma associated with cva

20) Confidence 0.46 Published 2008 Journal Vascular Health and Risk Management Section Body Doc Link PMC2663435 Disease Relevance 0.48 Pain Relevance 0.13

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