INT134754

Context Info Confidence 0.49 First Reported 2002 Last Reported 2009 Negated 0 Speculated 0 Reported most in Body Documents 9 Total Number 9 Disease Relevance 4.75 Pain Relevance 0.72

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

Anatomy Link Frequency extracellular matrix 4 blood 2 venules 2 PLAT (Homo sapiens)

Pain Link Frequency Relevance Heat ischemia 15 96.40 cocaine 140 94.56 cva 23 88.20 Inflammation 42 86.96 antagonist 5 78.00 adenocard 6 64.56 Somatostatin 5 57.36 metalloproteinase 4 50.00 cytokine 19 40.52 Inflammatory response 6 25.68

Disease Link Frequency Relevance Heat Increased Venous Pressure Under Development 66 99.96 Diabetes Mellitus 271 97.88 Cv Unclassified Under Development 15 96.40 Renal Disease 6 96.04 Rupture 4 95.72 Atherosclerosis 36 95.20 Amyloid Plaque 7 94.32 Thrombophilia 4 93.92 Thrombosis 19 89.08 Diabetes Mellitus-type I 2 88.24

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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).

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

1) Confidence 0.49 Published 2007 Journal Vascular Health and Risk Management Section Body Doc Link PMC2350146 Disease Relevance 1.64 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).

Positive_regulation (increased) of Gene_expression (expression) of tissue plasminogen activator in extracellular matrix

2) Confidence 0.45 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).

Positive_regulation (increased) of Gene_expression (expression) of PLAT in extracellular matrix

3) Confidence 0.45 Published 2006 Journal Clin. Pharmacol. Ther. Section Body Doc Link 16580899 Disease Relevance 0.14 Pain Relevance 0

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).

Positive_regulation (increase) of Gene_expression (groups) of tPA in venules

4) Confidence 0.41 Published 2002 Journal BMC Cardiovasc Disord Section Body Doc Link PMC117121 Disease Relevance 0.15 Pain Relevance 0.05

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).

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

5) Confidence 0.36 Published 2008 Journal Vascular Health and Risk Management Section Body Doc Link PMC2663449 Disease Relevance 1.21 Pain Relevance 0.04

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.

Positive_regulation (increased) of Gene_expression (expression) of tPA

6) Confidence 0.35 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2553267 Disease Relevance 0.31 Pain Relevance 0.09

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.

Positive_regulation (leads) of Gene_expression (expression) of tPA associated with rupture

7) Confidence 0.35 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2553267 Disease Relevance 0.30 Pain Relevance 0.07

The biochemical pathway for thrombolysis is such that tissue plasminogen activator coverts plaminogen to plasmin which in turn causes fibrinolysis by degrading fibrinogen and fibrin clots.

Positive_regulation (coverts) of Gene_expression (coverts) of tissue plasminogen activator

8) Confidence 0.30 Published 2007 Journal Subst Abuse Treat Prev Policy Section Body Doc Link PMC2042971 Disease Relevance 0.31 Pain Relevance 0.36

Stimulation of plasminogen through tPA (tissue plasminogen activator) and the subsequent generation of plasmin reduces ?

Positive_regulation (Stimulation) of Gene_expression (through) of tPA

9) Confidence 0.07 Published 2009 Journal The Open Neurology Journal Section Body Doc Link PMC2684708 Disease Relevance 0.46 Pain Relevance 0.12

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