Angiogenesis in the progression of non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent liver disease worldwide, and an increasing cause of liver cirrhosis and hepatocellular carcinoma. Angiogenesis, the formation of new blood vessels from pre-existing ones, is a key pathophysiological mechanism contributing to NAFLD progression. Major triggers for angiogenesis in NAFLD include tissue hypoxia, structural and dynamic endothelial cell dysfunction, stellate cell activation and macrophage-mediated inflammation. In turn, angiogenesis drives inflammation and is closely linked to the progression of liver fibrosis and the development of liver cancer. In particular, the molecular crosstalk between pro-angiogenic endothelial cells and activated stellate cells can result in a positive feedback loop in which angiogenesis and fibrosis develop in parallel. In this review, we highlight the molecular mechanisms, drivers and consequences of angiogenesis in the progression of NAFLD to NASH, fibrosis and hepatocellular carcinoma. Evidence from animal and clinical studies suggests that mediators of angiogenesis and endothelial dysfunction are promising disease biomarkers, and that inhibiting angiogenesis may improve the course of NAFLD.

Keywords: NASH, HCC, angiopoietin-2, endothelial dysfunction, stellate cell.