Mechanisms of angiocrine signaling in the liver

1Vascular Oncology and Metastasis, German Cancer Research Center, Heidelberg (DKFZ-ZMBH Alliance); 2Vascular Biology and Tumor Angiogenesis, Medical Faculty Mannheim (CBTM), Heidelberg University; 3German Cancer Consortium... [ view full abstract ]

¹Vascular Oncology and Metastasis, German Cancer Research Center, Heidelberg (DKFZ-ZMBH Alliance); ²Vascular Biology and Tumor Angiogenesis, Medical Faculty Mannheim (CBTM), Heidelberg University; ³German Cancer Consortium (DKTK) Heidelberg, Germany

Blood vessels form one of the body’s largest surfaces serving as critical interface between the circulation and the different organ environments. They thereby don’t just support rheological functions, but act through paracrine (angiocrine) cytokines as gatekeeper of tissue homeostasis and adaptation to pathologic challenge. The liver with its two vascular beds - the arterial and the sinusoidal vasculature - has emerged as a prototypic organ to study the mechanisms of angiocrine signaling. During development, endothelial programs involving GATA4 and other transcription factors orchestrate liver organogenesis. EC-derived Wnt signals act angiocrine and provide positional cues controlling liver zonation. Likewise, EC-derived cytokines control hepatocyte proliferation during liver regeneration. This presentation summarizes the state-of-the-art of endothelial angiocrine signaling in the liver and presents new data showing that angiocrine signals are not just EC-derived, but that hepatic stellate cells similarly control liver regeneration, fibrosis and heptocarcinogensis in an angiocrine manner.