Compartment-specific expression of plasminogen activator inhibitor-1 correlates with severity/outcome of murine polymicrobial sepsis. 
Plasminogen activator inhibitor type 1 (PAI-1) co-induces septic coagulopathy.  We aimed to characterize spatiotemporal PAI-1 gene/protein changes occurring in acute sepsis and tested whether PAI-1 fluctuations correlate with sepsis severity and early outcome.  Female mice underwent cecal ligation and puncture (CLP) in three experiments.  I: mild (23 G needle) CLP to compare circulating PAI-1 to its organ gene expression within 0-24h.  II: mild or severe (17 G) CLP to asses differences in PAI-1 organ-specific expression and in coagulation/fibrinolysis.  III: moderate (18 G) CLP to characterize circulating PAI-1 in survivors (SUR), and to retrospectively compare it to dying (DIE) mice.  In mild sepsis, the trajectory of circulating PAI-1 (1089 ng/ml peak at 24h) was identical to PAI-1 gene expression in the left cranial vena cava (LCVC; 39-fold peak at 24h).  PAI-1 expression rise was immediate (60-fold at 6h) and sustained in the liver, but marginal in the kidney, lungs and heart.  Body temperature decrease correlated with the PAI-1 expression increase in the liver (rho = -0.79), and blood (protein, rho = -0.53).  Regardless of severity, PAI-1 gene expression remained unaltered except the LCVC where it was >3-fold higher in 17G (vs. 23 G).  Severe sepsis extended activated partial thromboplastin/pro-thrombin time and increased circulating PAI-1, while antithrombin and fibrinogen decreased at 6 and/or 24h (vs. 23 G).  Within 24h of death, circulating PAI-1 in DIE was >3-fold higher versus SUR.  Polymicrobial sepsis caused a gradual circulating PAI-1 release and highly variable gene expression response pattern in organs.  Only circulating PAI-1 and PAI-1 expression in the LCVC correlated with response severity and/or outcome.