Endothelial Cell-Derived Angiopoietin-2 Controls Liver Regeneration as a Spatiotemporal Rheostat

Vessels provide the conduits that deliver metabolites and oxygen to the tissue and export waste products. After ischemia or tissue injury, endothelial cells migrate and proliferate to re-establish the capillary network in a process termed angiogenesis to maintain oxygen supply. Besides these essential and well-established functions in oxygen delivery, recent studies suggest that endothelial cells contribute to the multicellular-crosstalk that balanc-es regeneration and dysfunctional or maladaptive healing. Thus, endothelial cells not only seem important for oxygen delivery but act as paracrine source for signals that deter-mine tissue regeneration versus fibrosis. The interaction of endothelial-derived signals with hepatocyte functions has already been shown in the development of model organ-isms such as zebrafish1 and more recently during regen-eration of lung and liver in adult mice.2,