Boteon YL, Laing R, Mergental H, Reynolds GM, Mirza DF, Afford SC, Bhogal RH. Mechanisms of autophagy activation in endothelial cell and their targeting during normothermic machine liver perfusion. World J Gastroenterol 2017; 23(48): 8443-8451 [PMID: 29358854 DOI: 10.3748/wjg.v23.i48.8443]
Corresponding Author of This Article
Dr. Ricky H Bhogal, the Centre for Liver Research, Institute for Biomedical Research, University of Birmingham, Birmingham B15 2TT, United Kingdom. ricky.bhogal@uhb.nhs.uk
Research Domain of This Article
Surgery
Article-Type of This Article
Minireviews
Open-Access Policy of This Article
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/
World J Gastroenterol. Dec 28, 2017; 23(48): 8443-8451 Published online Dec 28, 2017. doi: 10.3748/wjg.v23.i48.8443
Mechanisms of autophagy activation in endothelial cell and their targeting during normothermic machine liver perfusion
Yuri L Boteon, Richard Laing, Hynek Mergental, Gary M Reynolds, Darius F Mirza, Simon C Afford, Ricky H Bhogal
Yuri L Boteon, Richard Laing, Hynek Mergental, Darius F Mirza, Ricky H Bhogal, The Liver Unit, University Hospitals of Birmingham, Mindelsohn Way, Edgbaston, Birmingham B15 2TT, United Kingdom
Yuri L Boteon, Richard Laing, Hynek Mergental, Gary M Reynolds, Darius F Mirza, Simon C Afford, Ricky H Bhogal, The Centre for Liver Research, Centre for Liver Research, National Institute for Health Research (NIHR) Birmingham Biomedical Research Centre, Institute for Biomedical Research, University of Birmingham, Birmingham B15 2TT, United Kingdom
Author contributions: Boteon YL and Bhogal RH wrote the manuscript; Mergental H, Mirza DF and Afford SC critically appraised the manuscript; Reynolds GM performed the immunohistochemistry; Bhogal RH formatted and edited the final manuscript.
Conflict-of-interest statement: No potential conflicts of interest relevant to this article were reported.
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. Ricky H Bhogal, the Centre for Liver Research, Institute for Biomedical Research, University of Birmingham, Birmingham B15 2TT, United Kingdom. ricky.bhogal@uhb.nhs.uk
Telephone: +44-121-4155739
Received: May 1, 2017 Peer-review started: May 5, 2017 First decision: June 7, 2017 Revised: June 19, 2017 Accepted: July 12, 2017 Article in press: July 12, 2017 Published online: December 28, 2017
Abstract
Ischaemia-reperfusion injury (IRI) is the leading cause of injury seen in the liver following transplantation. IRI also causes injury following liver surgery and haemodynamic shock. The first cells within the liver to be injured by IRI are the liver sinusoidal endothelial cells (LSEC). Recent evidence suggests that LSEC co-ordinate and regulates the livers response to a variety of injuries. It is becoming increasingly apparent that the cyto-protective cellular process of autophagy is a key regulator of IRI. In particular LSEC autophagy may be an essential gatekeeper to the development of IRI. The recent availability of liver perfusion devices has allowed for the therapeutic targeting of autophagy to reduce IRI. In particular normothermic machine liver perfusion (NMP-L) allow the delivery of pharmacological agents to donor livers whilst maintaining physiological temperature and hepatic flow rates. In this review we summarise the current understanding of endothelial autophagy and how this may be manipulated during NMP-L to reduce liver IRI.
Core tip: Liver sinusoidal endothelial cells autophagy regulates liver ischaemia reperfusion injury and this process can be targeted for therapeutic benefit using normothermic machine liver perfusion.
