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Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Mar 27, 2015; 7(3): 443-459
Published online Mar 27, 2015. doi: 10.4254/wjh.v7.i3.443
Endothelial dysfunction in cirrhosis: Role of inflammation and oxidative stress
Balasubramaniyan Vairappan
Balasubramaniyan Vairappan, Department of Biochemistry, Jawaharlal Institute of Postgraduate Medical Education and Research, Pondicherry 605006, India
Author contributions: Vairappan B solely contributed this work.
Supported by The Department of Biotechnology-Ramalingaswami Fellowship 5 years grant from the Government of India.
Conflict-of-interest: Vairappan B declares that he has no conflict of interest.
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: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Dr. Balasubramaniyan Vairappan, Assistant Professor, Department of Biochemistry, Jawaharlal Institute of Postgraduate Medical Education and Research, Dhanvantri Nagar, Gorimedu, Pondicherry 605006, India. balamaniyan@gmail.com
Telephone: +91-413-2298531 Fax: +91-960-0461977
Received: August 29, 2014
Peer-review started: August 30, 2014
First decision: November 1, 2014
Revised: November 8, 2014
Accepted: November 27, 2014
Article in press: November 27, 2014
Published online: March 27, 2015
Processing time: 214 Days and 13 Hours
Abstract

This review describes the recent developments in the pathobiology of endothelial dysfunction (ED) in the context of cirrhosis with portal hypertension and defines novel strategies and potential targets for therapy. ED has prognostic implications by predicting unfavourable early hepatic events and mortality in patients with portal hypertension and advanced liver diseases. ED characterised by an impaired bioactivity of nitric oxide (NO) within the hepatic circulation and is mainly due to decreased bioavailability of NO and accelerated degradation of NO with reactive oxygen species. Furthermore, elevated inflammatory markers also inhibit NO synthesis and causes ED in cirrhotic liver. Therefore, improvement of NO availability in the hepatic circulation can be beneficial for the improvement of endothelial dysfunction and associated portal hypertension in patients with cirrhosis. Furthermore, therapeutic agents that are identified in increasing NO bioavailability through improvement of hepatic endothelial nitric oxide synthase (eNOS) activity and reduction in hepatic asymmetric dimethylarginine, an endogenous modulator of eNOS and a key mediator of elevated intrahepatic vascular tone in cirrhosis would be interesting therapeutic approaches in patients with endothelial dysfunction and portal hypertension in advanced liver diseases.

Keywords: Asymmetric dimethylarginine; Endothelial function; Nitric oxide; Portal hypertension; Hepatic cirrhosis, Reactive oxygen species; Inflammation

Core tip: Endothelial dysfunction (ED) is a key and early relentless event in patients suffering from gastrointestinal bleeding in cirrhosis and involves in response to both vasoactive and vasoconstrictor substances. The one such vasoactive molecule, nitric oxide (NO) plays a prime role in maintaining normal hepatic vascular function and if there any defect in NO availability leads to ED and portal hypertension (PHT) could be of great utility in preventing and curing complications of PHT.