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ORIGINAL RESEARCH article

Front. Cell Dev. Biol.
Sec. Cell Death and Survival
Volume 12 - 2024 | doi: 10.3389/fcell.2024.1455258
This article is part of the Research Topic Unraveling Ischemia-Reperfusion Injury: Advances in Injury Mechanisms and Treatment Targets View all articles

Relevance of the GH-VEGFB/VEGFA axis in liver grafts from braindead donors with alcohol-associated liver disease

Provisionally accepted
Marc Micó-Carnero Marc Micó-Carnero 1,2Carlos Rojano-Alfonso Carlos Rojano-Alfonso 1,2Cristina Maroto-Serrat Cristina Maroto-Serrat 1,2Juan Carlos Cutrin Juan Carlos Cutrin 3ARANI CASILLAS-RAMIREZ ARANI CASILLAS-RAMIREZ 4,5*Carmen Peralta Carmen Peralta 1*
  • 1 August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Barcelona, Spain
  • 2 University of Barcelona, Barcelona, Catalonia, Spain
  • 3 Molecular Biotechnology Center, Department of Molecular Biotechnology and Health Sciences, School of Medicine, University of Turin, Torino, Piedmont, Italy
  • 4 Hospital Regional De Alta Especialidad de Cd. Victoria, Ciudad Victoria, Tamaulipas4, Mexico
  • 5 Facultad de Medicina e Ingeniería en Sistemas Computacionales Matamoros, Universidad Autónoma de Tamaulipas, Tapaulimas, Mexico

The final, formatted version of the article will be published soon.

    Grafts with alcohol-associated liver disease (ALD) subjected to prolonged cold ischaemia from donors after brain death (DBD) are typically unsuitable for transplantation. Here, we investigated the role of growth hormone (GH) in livers with ALD from DBDs and its relationship with vascular endothelial growth factor A (VEGFA) and VEGFB. Livers from rats fed ethanol for 6 weeks and with brain death (BD) were cold stored for 24 h and subjected to ex vivo reperfusion. Hepatic damage and proliferative and inflammatory parameters were analysed after BD, before graft retrieval, and after reperfusion. Survival was monitored using an in vivo transplantation model. In DBDs, the administration of GH, which increased the levels in the intestine but not in the liver, induced the generation of both VEGFA and VEGFB in the intestine and protected against hepatic damage caused by BD before retrieving liver grafts from donors. However, VEGFA was the only factor that protected against damage after cold ischemia and reperfusion, which also increased the survival of the recipients. In conclusion, the signalling pathway and beneficial properties of the GH-VEGFA/VEGFB pathway, in which the intestine-liver axis plays a key role, were disrupted when grafts with ALD from DBDs were retrieved from donors and subjected to cold ischemia and reperfusion.

    Keywords: Liver Transplantation, Brain Death, ALD, Ischemia-reperfusion, Growth Hormone, VEGF

    Received: 26 Jun 2024; Accepted: 16 Dec 2024.

    Copyright: © 2024 Micó-Carnero, Rojano-Alfonso, Maroto-Serrat, Cutrin, CASILLAS-RAMIREZ and Peralta. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    ARANI CASILLAS-RAMIREZ, Hospital Regional De Alta Especialidad de Cd. Victoria, Ciudad Victoria, Tamaulipas4, Mexico
    Carmen Peralta, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, 08036, Barcelona, Spain

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