title: PAI-1 plays an important role in liver failure after excessive hepatectomy in the rat.
abstract: OBJECTIVE
  Well-organized turnover of the extracellular matrix is important in liver regeneration, which is regulated by the plasminogen activating system. The aim of this study was to investigate the role of plasminogen activator inhibitor-1 (PAI-1) after excessive hepatectomy and to ascertain whether angiotensin-converting enzyme (ACE) inhibitors, which are PAI-1 inhibitors as well, successfully improve the survival rate of rats that have undergone 95% partial hepatectomy (PHx).
  
  
  METHODS
  Using liver tissues sampled after 90% or 95% PHx, the expression of PAI-1 mRNA was evaluated using reverse transcription polymerase chain reaction. Hepatic PAI-1 protein and urokinase-type plasminogen activator (uPA) levels were determined by enzyme-linked immunosorbent assay. Survival study and cytodynamic analysis by 5-bromo-2'-deoxyuridine staining were performed to evaluate the effects of ACE inhibition.
  
  
  RESULTS
  The levels of PAI-1 mRNA and hepatic PAI-1 protein in the 95% PHx group peaked and were then maintained. By contrast, the uPA level fell relative to the 90% PHx group. Additionally, the hepatic PAI-1 protein level decreased and the survival rate improved in the 95% PHx rats that had undergone ACE inhibition.
  
  
  CONCLUSIONS
  Our experimental results suggest that PAI-1 plays a role in the occurrence of liver failure after excessive hepatectomy via accelerated maturation of pro-uPA and fibrinolytic factors. These are potential molecular therapeutic targets for liver failure after excessive hepatectomy.
authors.affiliation: Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Kazuteru
authors.initials: K
authors.lastname: Watanabe
authors.forename: Shinji
authors.initials: S
authors.lastname: Togo
authors.forename: Takuji
authors.initials: T
authors.lastname: Takahashi
authors.forename: Ryusei
authors.initials: R
authors.lastname: Matsuyama
authors.forename: Harumi
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Shimizu
authors.forename: Hirochika
authors.initials: H
authors.lastname: Makino
authors.forename: Kenichi
authors.initials: K
authors.lastname: Matsuo
authors.forename: Daisuke
authors.initials: D
authors.lastname: Morioka
authors.forename: Toru
authors.initials: T
authors.lastname: Kubota
authors.forename: Yoji
authors.initials: Y
authors.lastname: Nagashima
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shimada
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D006498:Hepatectomy / Q000009:adverse effects*; D048289:Imidazolidines / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000601:surgery; D017093:Liver Failure / Q000209:etiology* / Q000378:metabolism*; D008297:Male; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015996:Survival Rate; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D048289:Imidazolidines; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; C065166:imidapril; D014568:Urokinase-Type Plasminogen Activator