Early genetic responses in rat vascular tissue after simulated diving

2012 ◽  
Vol 44 (24) ◽  
pp. 1201-1207 ◽  
Author(s):  
Ingrid Eftedal ◽  
Arve Jørgensen ◽  
Ragnhild Røsbjørgen ◽  
Arnar Flatberg ◽  
Alf O. Brubakk
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Plasminogen Activator ◽  
Differential Gene Expression ◽  
Vascular Function ◽  
Plasminogen Activator Inhibitor ◽  
Fine Tuning ◽  
Plasminogen Activator Inhibitor 1 ◽  
Differential Gene ◽  
Activator Inhibitor

Diving causes a transient reduction of vascular function, but the mechanisms behind this are largely unknown. The aim of this study was therefore to analyze genetic reactions that may be involved in acute changes of vascular function in divers. Rats were exposed to 709 kPa of hyperbaric air (149 kPa Po2) for 50 min followed by postdive monitoring of vascular bubble formation and full genome microarray analysis of the aorta from diving rats ( n = 8) and unexposed controls ( n = 9). Upregulation of 23 genes was observed 1 h after simulated diving. The differential gene expression was characteristic of cellular responses to oxidative stress, with functions of upregulated genes including activation and fine-tuning of stress-responsive transcription, cytokine/cytokine receptor signaling, molecular chaperoning, and coagulation. By qRT-PCR, we verified increased transcription of neuron-derived orphan receptor-1 ( Nr4a3), plasminogen activator inhibitor 1 ( Serpine1), cytokine TWEAK receptor FN14 ( Tnfrsf12a), transcription factor class E basic helix-loop-helix protein 40 ( Bhlhe40), and adrenomedullin ( Adm). Hypoxia-inducible transcription factor HIF1 subunit HIF1-α was stabilized in the aorta 1 h after diving, and after 4 h there was a fivefold increase in total protein levels of the procoagulant plasminogen activator inhibitor 1 (PAI1) in blood plasma from diving rats. The study did not have sufficient power for individual assessment of effects of hyperoxia and decompression-induced bubbles on postdive gene expression. However, differential gene expression in rats without venous bubbles was similar to that of all the diving rats, indicating that elevated Po2 instigated the observed genetic reactions.

Bezafibrate Induces Plasminogen Activator Inhibitor-1 Gene Expression in a CLOCK-Dependent Circadian Manner

2010 ◽  
Vol 78 (1) ◽  
pp. 135-141 ◽  
Author(s):  
Katsutaka Oishi ◽  
Satoru Koyanagi ◽  
Naoya Matsunaga ◽  
Koji Kadota ◽  
Eriko Ikeda ◽  
...  
Keyword(s):  
Gene Expression ◽  
Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
Plasminogen Activator Inhibitor 1 ◽  
Activator Inhibitor

scholarly journals Insulin Inhibits the Pro-Inflammatory Transcription Factor Early Growth Response Gene-1 (Egr)-1 Expression in Mononuclear Cells (MNC) and Reduces Plasma Tissue Factor (TF) and Plasminogen Activator Inhibitor-1 (PAI-1) Concentrations

2002 ◽  
Vol 87 (3) ◽  
pp. 1419-1422 ◽  
Author(s):  
Ahmad Aljada ◽  
Husam Ghanim ◽  
Priya Mohanty ◽  
Neeti Kapur ◽  
Paresh Dandona
Keyword(s):  
Transcription Factor ◽  
Tissue Factor ◽  
Plasminogen Activator ◽  
Growth Response ◽  
Plasminogen Activator Inhibitor ◽  
Early Growth ◽  
Plasminogen Activator Inhibitor 1 ◽  
Early Growth Response ◽  
Activator Inhibitor ◽  
Pai 1

We have recently demonstrated that an infusion of a low dose of insulin reduces the intranuclear NF-κB (a pro-inflammatory transcription factor) content in MNC while also reducing the p;asma concentration of NF-κB dependent pro-inflammatory cytokines and adhesion molecules. We have now tested the effect of insulin on the pro-inflammatory transcription factor, early growth response-1 (Egr-1) and plasma concentration of tissue factor (TF) and plasminogen activator inhibitor-1 (PAI-1), two major proteins whose expression is modulated by Egr-1. Insulin was infused at the rate of 2 IU/h in 5% dextrose (100 mL/h) and KCI (8 mmol/h) for 4 h in the fasting state in ten obese subjects. Blood samples were obtained at 0, 2, 4 and 6 h. MNC were isolated and their total homogenates and nuclear fractions were prepared and Egr-1 was measured by electrophoretic mobility shift assay (EMSA). Plasma TF and PAI-1 were assayed by ELISA. There was a significant fall in Egr-1 at 2 (66 ± 14% of basal level) and 4 h (47± 17% of the basal level; P<0.01). PAI-1 levels (basal = 100%) decreased significantly after insulin infusion at 2 h (57 ± 6.7% of the basal level) and at 4 h (58 ± 8.3% of the basal level; P<0.001). Plasma TF levels (basal = 100%) decreased to 76 ± 7.7% of the basal level at 2 h and to 85 ± 10.4% of the basal level at 4 h (P<0.05). Thus, insulin reduces intranuclear Egr-1 and the expression of TF and PAI-1. These data provide further evidence that insulin has an anti-inflammatory effect including the inhibition of TF and PAI-1 expression. These effects suggest a potential beneficial effect of insulin in thrombin formation and fibrinolysis in atherothrombosis.

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