Role of Angiogenesis in the Pathogenesis of NAFLD

Figure 1. Mechanisms promoting angiogenesis in NAFLD and effects of antiangiogenic treatments in animal models. In NAFLD, steatotic hepatocytes produce proangiogenic extracellular vesicles. Steatosis induces hypoxia both by an increased lipid metabolism which enhances oxygen consumption and by a mechanical pressure on sinusoids. Hepatic stellate cells, portal myofibroblasts and macrophages stimulate angiogenesis by secreting VEGF. Proangiogenic signals also come from the adipose tissue which secretes leptin. In animal models of NAFLD, several antiangiogenic treatments (anti-VEGR2, L1-10 peptibody, angiotensin II receptor blockers) have shown efficacy to reduce steatosis, inflammation, fibrosis and HCC. Abbreviations: HCC, hepatocellular carcinoma; LSECs, liver sinusoidal endothelial cells; NAFLD, non-alcoholic fatty liver disease; VEGF, vascular endothelial growth factor; VEGFR-2, vascular endothelial growth factor receptor-2.