Sinusoidal endothelial cell proliferation and expression of angiopoietin/Tie family in regenerating rat liver

Background/Aims: Angiogenesis is essential in liver regeneration, However, only little is known about sinusoidal endothelial cell proliferation and th e role of different angiogenic growth factors and their receptors during re generation. Methods: Seventy percent hepatectomy was carried out on male rats, Serial c hanges in endothelial cell proliferation were evaluated by immunohistochemi stry. The mRNA expressions of angiogenic growth factors (vascular endotheli al growth factor (VEGF) and angiopoietins 1 and 2) and their receptors (flt -1, flk-1, Tie-1 and Tie-2) in the whole liver were evaluated by semi-quant itative RT-PCR, Results: Significant elevation of endothelial cell proliferation started at 48 h and peaked at 72 h after hepatectomy. The ratio of sinusoids to liver tissue area initially decreased at 72 h, and thereafter, significantly inc reased at 96 h. VEGF related factors had early peaks, which coincided with the endothelial proliferation. flt-1, flk-1 and VEGF expressions peaked at 24, 48 and 72 h, respectively, angiopoietin/Tie factors peaked at 96 h, exc ept Ang-2, which gradually increased and peaked at 168 h. Conclusions: During liver regeneration, hepatocyte proliferation was follow ed by endothelial cell proliferation. The VEGF family and angiopoietin/Tie system may have distinct roles in angiogenesis, with an enhanced expression of the VEGF family in the early phase of regeneration followed by angiopoi etin/Tie expression. (C) 2001 European Association for the Study of the Liv er, Published by Elsevier Science B,V, All rights reserved.