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World J Hepatol. Mar 27, 2015; 7(3): 377-391
Published online Mar 27, 2015. doi: 10.4254/wjh.v7.i3.377
Angiogenesis and liver fibrosis
Gülsüm Özlem Elpek
Gülsüm Özlem Elpek, Department of Pathology, Akdeniz University Medical School, 07070 Antalya, Turkey
Author contributions: Elpek GO solely analyzed the data and wrote the paper.
Conflict-of-interest: The authors declare that they have no competing interests.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Gülsüm Özlem Elpek, MD, Professor, Department of Pathology, Akdeniz University Medical School, Dumlupınar Bulvarı, 07070 Antalya, Turkey.
Telephone: +90-242-2496389 Fax: +90-242-2275540
Received: August 28, 2014
Peer-review started: August 28, 2014
First decision: September 19, 2014
Revised: November 10, 2014
Accepted: November 27, 2014
Article in press: November 27, 2014
Published online: March 27, 2015

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.