title: Compartment-specific expression of plasminogen activator inhibitor-1 correlates with severity/outcome of murine polymicrobial sepsis.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Ludwig Boltzmann Institute for Experimental and Clinical Traumatology in the Trauma Research Center of the AUVA, Vienna, Austria.
authors.forename: Pierre
authors.initials: P
authors.lastname: Raeven
authors.forename: Georg Alexander
authors.initials: GA
authors.lastname: Feichtinger
authors.forename: Katrin Maria
authors.initials: KM
authors.lastname: Weixelbaumer
authors.forename: Simone
authors.initials: S
authors.lastname: Atzenhofer
authors.forename: Heinz
authors.initials: H
authors.lastname: Redl
authors.forename: Martijn
authors.initials: M
authors.lastname: Van Griensven
authors.forename: Soheyl
authors.initials: S
authors.lastname: Bahrami
authors.forename: Marcin Filip
authors.initials: MF
authors.lastname: Osuchowski
mesh_terms: D000818:Animals; D005260:Female; D005342:Fibrinolysis / Q000502:physiology; D015870:Gene Expression; D051379:Mice; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D018805:Sepsis / Q000097:blood / Q000235:genetics / Q000378:metabolism* / Q000382:microbiology; D016896:Treatment Outcome
chemical_list: D017395:Plasminogen Activator Inhibitor 1