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Mechanisms of autophagy activation in endothelial cell and their targeting during normothermic machine liver

Yuri L Boteon1, Richard Laing1, Hynek Mergental1

  • 1The Liver Unit, University Hospitals of Birmingham, Mindelsohn Way, Edgbaston, Birmingham B15 2TT, United Kingdom.

World Journal of Gastroenterology
|January 24, 2018
PubMed

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.

Keywords:
AutophagyIschaemia-reperfusion injuryLiver transplantNormothermic machine liver perfusion

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