R.H.L. and F.L. jointly coordinated this work.
1538-7836/asset/olbannerleft.gif?v=1&s=77e14c4c55f90ae6eb6fec99ac201108f7c92510)
1538-7836/asset/olbannerright.gif?v=1&s=87cd273ca1fd9dc5d95b1da3d90fa3ee7637f329)
ORIGINAL ARTICLE
You have free access to this content
Plasmin-dependent proteolysis of tissue factor pathway inhibitor in a mouse model of endotoxemia
Article first published online: 27 JAN 2013
DOI: 10.1111/jth.12044
© 2012 International Society on Thrombosis and Haemostasis
Additional Information
How to Cite
LUPU, C., HERLEA, O., TANG, H., LIJNEN, R. H. and LUPU, F. (2013), Plasmin-dependent proteolysis of tissue factor pathway inhibitor in a mouse model of endotoxemia. Journal of Thrombosis and Haemostasis, 11: 142–148. doi: 10.1111/jth.12044
- †
R.H.L. and F.L. jointly coordinated this work.
Publication History
- Issue published online: 27 JAN 2013
- Article first published online: 27 JAN 2013
- Accepted manuscript online: 26 OCT 2012 11:01AM EST
- Received 8 December 2011, accepted 13 October 2012
- Abstract
- Article
- References
- Cited By
Keywords:
- endotoxin;
- lung;
- plasmin;
- plasminogen-activating system-deficient mice;
- tissue factor pathway inhibitor
Summary. Background: The development of a procoagulant state in sepsis, owing to aberrant expression of tissue factor (TF) and a sharp decrease in the level of its major inhibitor, TF pathway inhibitor (TFPI), could lead to microthrombotic organ failure. The mechanism for the decline in TFPI activity in the lung could involve plasmin-mediated cleavage of the inhibitor. Objective: To investigate the effect of plasmin generation on lung-associated TFPI activity, in normal conditions and during infusion of endotoxin (lipopolysaccharide [LPS]) in mice. Methods: Plasmin generation and TFPI activity were assayed in the lungs of mice deficient in tissue-type plasminogen (Plg) activator (t-PA) or Plg, at 2 h after LPS or saline injection. Results: The sharp loss of lung-associated TFPI activity at 2 h after LPS challenge paralleled the abrupt increase in plasmin generation. TFPI activity was significantly retained in both t-PA−/− and Plg−/− mice, which are unable to generate plasmin. Conclusion: The increased plasmin generation during the early stages of sepsis could cleave/inactivate TFPI and thus lead to thrombotic complications.