These authors contributed equally to this work.
Plasminogen mediates liver regeneration and angiogenesis after experimental partial hepatectomy
Article first published online: 3 OCT 2003
Copyright © 2003 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.
British Journal of Surgery
Volume 90, Issue 11, pages 1384–1390, November 2003
How to Cite
Drixler, T. A., Vogten, J. M., Gebbink, M. F. B. G., Carmeliet, P., Voest, E. E. and Borel Rinkes, I. H. M. (2003), Plasminogen mediates liver regeneration and angiogenesis after experimental partial hepatectomy. Br J Surg, 90: 1384–1390. doi: 10.1002/bjs.4275
- Issue published online: 27 OCT 2003
- Article first published online: 3 OCT 2003
- Manuscript Accepted: 1 APR 2003
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).
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.
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.
Plasminogen and uPA are essential for optimal liver regeneration. In addition, plasminogen appears to be a major determinant in regeneration-associated hepatic angiogenesis. Copyright © 2003 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.