Angiogenesis in chronic liver disease and its complications

Liver Int. 2011 Feb;31(2):146-62. doi: 10.1111/j.1478-3231.2010.02369.x. Epub 2010 Nov 15.


Nowadays, liver cancer, cirrhosis and other liver-related diseases are the fifth most common cause of mortality in the UK. Furthermore, chronic liver diseases (CLDs) are one of the major causes of death, which are still increasing year-on-year. Therefore, knowledge about the pathophysiology of CLDs and its complications is of uttermost importance. The goal of this review is to clarify the role of angiogenesis in the disease progression of various liver diseases. Looking closer at the pathophysiology of portal hypertension (PH), fibrosis, cirrhosis, non-alcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC), we find that angiogenesis is a recurring factor in the disease progression. In PH, several factors involved in its pathogenesis, such as hypoxia, oxidative stress, inflammation and shear stress are potential mediators for the angiogenic response. The progression from fibrosis to cirrhosis, the end-point of CLDs, is distinguished by a prolonged inflammatory and fibrogenic process that leads to an abnormal angioarchitecture distinctive for cirrhosis. In several stages of NASH, a link might be made between the disease progression and hepatic microvasculature changes. HCC is one of the most vascular solid tumours in which angiogenesis plays an important role in its development, progression and metastasis. The close relationship between the progression of CLDs and angiogenesis emphasises the need for anti-angiogenic therapy as a tool for blocking or slowing down the disease progression. The fact that angiogenesis plays a pivotal role in CLDs gives rise to new opportunities for treating CLDs and its complications.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Angiogenesis Inhibitors / therapeutic use
  • Angiopoietins / metabolism
  • Angiostatins / metabolism
  • Cadherins / metabolism
  • Carcinoma, Hepatocellular / complications
  • Carcinoma, Hepatocellular / drug therapy
  • Carcinoma, Hepatocellular / physiopathology*
  • Chronic Disease
  • Disease Progression
  • Endostatins / metabolism
  • Fatty Liver / complications
  • Fatty Liver / physiopathology
  • Fibroblast Growth Factors / metabolism
  • Humans
  • Hypertension, Portal / complications
  • Hypertension, Portal / physiopathology*
  • Hypoxia-Inducible Factor 1 / metabolism
  • Integrins / metabolism
  • Liver Cirrhosis / complications
  • Liver Cirrhosis / physiopathology*
  • Liver Neoplasms / complications
  • Liver Neoplasms / drug therapy
  • Liver Neoplasms / physiopathology*
  • Microvessels / physiopathology*
  • Models, Biological*
  • Neovascularization, Pathologic / etiology
  • Neovascularization, Pathologic / physiopathology*
  • Non-alcoholic Fatty Liver Disease
  • Platelet-Derived Growth Factor / metabolism
  • Receptors, Vascular Endothelial Growth Factor / metabolism
  • Signal Transduction / physiology*
  • Thrombospondins / metabolism
  • Vascular Endothelial Growth Factor A / metabolism


  • Angiogenesis Inhibitors
  • Angiopoietins
  • Cadherins
  • Endostatins
  • Hypoxia-Inducible Factor 1
  • Integrins
  • Platelet-Derived Growth Factor
  • Thrombospondins
  • Vascular Endothelial Growth Factor A
  • Fibroblast Growth Factors
  • Angiostatins
  • Receptors, Vascular Endothelial Growth Factor