PAI-1 plays an important role in liver failure after excessive hepatectomy in the rat.
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.
Watanabe
Kazuteru
K
Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
Togo
Shinji
S
Takahashi
Takuji
T
Matsuyama
Ryusei
R
Yamamoto
Harumi
H
Shimizu
Tetsuya
T
Makino
Hirochika
H
Matsuo
Kenichi
K
Morioka
Daisuke
D
Kubota
Toru
T
Nagashima
Yoji
Y
Shimada
Hiroshi
H
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
D000806:Angiotensin-Converting Enzyme Inhibitors; D048289:Imidazolidines; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; C065166:imidapril; D014568:Urokinase-Type Plasminogen Activator