Plasminogen mediates liver regeneration and angiogenesis after experimental partial hepatectomy.
BACKGROUND
Plasmin system components are upregulated after partial hepatectomy, but their contribution to surgery-induced hepatic angiogenesis and regeneration is unclear. Liver regeneration and angiogenesis after partial hepatectomy were examined in mice lacking plasminogen or urokinase plasminogen activator (uPA).


METHODS
Mice with a single-gene deletion of plasminogen or uPA were subjected to 70 per cent partial hepatectomy. Liver regeneration was measured as relative liver weight and cell proliferation index. Angiogenesis was quantified by determining hepatic microvessel density after staining for sinusoidal endothelial cells.


RESULTS
The liver remnant weight was significantly reduced in mice lacking plasminogen or uPA compared with that in wild-type mice on days 2 and 7 after partial hepatectomy. This correlated with impaired cell proliferation. In wild-type mice, regeneration was accompanied by a significant increase in microvessel density after hepatectomy; this increase was impaired in plasminogen-deficient mice.


CONCLUSIONS
Plasminogen and uPA are essential for optimal liver regeneration. In addition, plasminogen appears to be a major determinant in regeneration-associated hepatic angiogenesis.
Department of Surgery, University Medical Centre Utrecht, Utrecht, The Netherlands.
T A
TA
Drixler
J M
JM
Vogten
M F B G
MF
Gebbink
P
P
Carmeliet
E E
EE
Voest
I H M
IH
Borel Rinkes
D000818:Animals; D002455:Cell Division / Q000502:physiology; D017353:Gene Deletion; D006498:Hepatectomy / Q000379:methods*; D008099:Liver / Q000033:anatomy & histology* / Q000098:blood supply; D008115:Liver Regeneration / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008833:Microcirculation / Q000502:physiology; D018919:Neovascularization, Physiologic / Q000502:physiology; D009929:Organ Size; D010958:Plasminogen / Q000235:genetics / Q000502:physiology*; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics / Q000502:physiology*
D010958:Plasminogen; D014568:Urokinase-Type Plasminogen Activator