The role of hepatic type 1 plasminogen activator inhibitor (PAI-1) during murine hemorrhagic shock

Claudio E. Lagoa, Yoram Vodovotz, Donna B. Stolz, Franck Lhuillier, Carol McCloskey, David Gallo, Runkuan Yang, Elena Ustinova, Mitchell P. Fink, Timothy R. Billiar, Wendy M. Mars*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

27 Scopus citations


Hemorrhagic shock (HS) followed by resuscitation (HS-R) is characterized by profound physiological changes. Even if the patient survives the initial blood loss, these poorly understood changes can lead to morbidity. One of the tissues most often affected is liver. We sought to recognize specific hepatic changes induced by this stressor to identify targets for therapeutic intervention. Gene array analyses using mouse liver mRNAs were used to identify candidate genes that contribute to hepatic damage. To verify the role of one of the genes identified using the arrays, mice were subjected to HS-R, and multiple parameters were analyzed. A profound increase in plasminogen activator inhibitor type 1 (PAI-1) mRNA was observed using hepatic mRNAs from C57B1/6 mice after HS, both with and without resuscitation. Constitutive loss of PAI-1 resulted in notable tissue preservation and lower (P < .05) alanine aminotransferase (ALT) levels. Fibrin degradation products (FDPs) and interleukins 6 and 10 (IL-6 and IL-10) were unaffected by loss of PAI-1; however, enhanced urokinase activity, an elevation of active hepatocyte growth factor (HGF), an increase in unprocessed transforming growth factor-β1 (TGF-β1), and retention of ERK phosphorylation after HS-R were associated with improved hepatic function. In conclusion. PAI-1 protein is a negative effector of hepatic damage after HS-R through its influence on classic regulators of hepatic growth, as opposed to its role in fibrinolysis.

Original languageEnglish
Pages (from-to)390-399
Number of pages10
Issue number2
StatePublished - Aug 2005
Externally publishedYes


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