Angiogenesis and liver fibrosis

Abstract

Recent data indicate that hepatic angiogenesis, regardless of the etiology, takes place in chronic liver diseases (CLDs) that are characterized by inflammation and progressive fibrosis. Because anti-angiogenic therapy has been found to be efficient in the prevention of fibrosis in experimental models of CLDs, it is suggested that blocking angiogenesis could be a promising therapeutic option in patients with advanced fibrosis. Consequently, efforts are being directed to revealing the mechanisms involved in angiogenesis during the progression of liver fibrosis. Literature evidences indicate that hepatic angiogenesis and fibrosis are closely related in both clinical and experimental conditions. Hypoxia is a major inducer of angiogenesis together with inflammation and hepatic stellate cells. These profibrogenic cells stand at the intersection between inflammation, angiogenesis and fibrosis and play also a pivotal role in angiogenesis. This review mainly focuses to give a clear view on the relevant features that communicate angiogenesis with progression of fibrosis in CLDs towards the-end point of cirrhosis that may be translated into future therapies. The pathogenesis of hepatic angiogenesis associated with portal hypertension, viral hepatitis, non-alcoholic fatty liver disease and alcoholic liver disease are also discussed to emphasize the various mechanisms involved in angiogenesis during liver fibrogenesis.

Keywords: Liver fibrosis; Angiogenesis; Cirrhosis; Fibrogenesis; Hepatic stellate cells; Vascular endothelial growth factor; Hypoxia; Chronic liver disease

Core tip: Hepatic angiogenesis is closely associated with the progression of fibrosis in chronic liver diseases (CLDs). Recent evidences demonstrated that blocking angiogenesis means also prevention of fibrosis progression. Hypoxia plays a crucial role in eliciting angiogenesis together with hepatic stellate cells being the most prominent sources of vascular endothelial growth factor and Angiopoietin-1. Adipokines, endoplasmic reticulum stress and related unfolded protein response; neuropilins; might be future therapeutical target in the progression of fibrosis in CLDs. Moreover studies on non-alcoholic steatohepatits demonstrated that of angiotensin and renin inhibitors could be effectively used as a new treatment strategy against angiogenesis in the prevention of fibrosis in CLDs.