Relevance of the GH-VEGFB/VEGFA axis in liver grafts from brain-dead donors with alcohol-associated liver disease
IntroductionGrafts 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...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2024.1455258/full |
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| author | Marc Micó-Carnero Marc Micó-Carnero Carlos Rojano-Alfonso Carlos Rojano-Alfonso Cristina Maroto-Serrat Cristina Maroto-Serrat Juan Carlos Cutrin Araní Casillas-Ramírez Araní Casillas-Ramírez Carmen Peralta |
| author_facet | Marc Micó-Carnero Marc Micó-Carnero Carlos Rojano-Alfonso Carlos Rojano-Alfonso Cristina Maroto-Serrat Cristina Maroto-Serrat Juan Carlos Cutrin Araní Casillas-Ramírez Araní Casillas-Ramírez Carmen Peralta |
| author_sort | Marc Micó-Carnero |
| collection | DOAJ |
| description | IntroductionGrafts 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.MethodsLivers 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.ResultsIn 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.DiscussionIn 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. |
| format | Article |
| id | doaj-art-521545b1b1dc4927928d1984f11e976f |
| institution | Kabale University |
| issn | 2296-634X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj-art-521545b1b1dc4927928d1984f11e976f2025-01-07T06:40:57ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2025-01-011210.3389/fcell.2024.14552581455258Relevance of the GH-VEGFB/VEGFA axis in liver grafts from brain-dead donors with alcohol-associated liver diseaseMarc Micó-Carnero0Marc Micó-Carnero1Carlos Rojano-Alfonso2Carlos Rojano-Alfonso3Cristina Maroto-Serrat4Cristina Maroto-Serrat5Juan Carlos Cutrin6Araní Casillas-Ramírez7Araní Casillas-Ramírez8Carmen Peralta9Department of Liver, Digestive System and Metabolism, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, SpainUniversitat de Barcelona, Barcelona, SpainDepartment of Liver, Digestive System and Metabolism, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, SpainUniversitat de Barcelona, Barcelona, SpainDepartment of Liver, Digestive System and Metabolism, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, SpainUniversitat de Barcelona, Barcelona, SpainMolecular Biotechnology Center II “Guido Tarone”, Department of Molecular Biotechnologies and Science for the Health, University of Torino, Torino, ItalyHospital Regional de Alta Especialidad de Ciudad Victoria, IMSS-BIENESTAR, Ciudad Victoria, MexicoFacultad de Medicina e Ingeniería en Sistemas Computacionales de Matamoros, Universidad Autónoma de Tamaulipas, Matamoros, MexicoDepartment of Liver, Digestive System and Metabolism, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, SpainIntroductionGrafts 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.MethodsLivers 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.ResultsIn 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.DiscussionIn 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.https://www.frontiersin.org/articles/10.3389/fcell.2024.1455258/fullliver transplantationbrain deathALDischemia-reperfusiongrowth hormoneVEGF |
| spellingShingle | Marc Micó-Carnero Marc Micó-Carnero Carlos Rojano-Alfonso Carlos Rojano-Alfonso Cristina Maroto-Serrat Cristina Maroto-Serrat Juan Carlos Cutrin Araní Casillas-Ramírez Araní Casillas-Ramírez Carmen Peralta Relevance of the GH-VEGFB/VEGFA axis in liver grafts from brain-dead donors with alcohol-associated liver disease Frontiers in Cell and Developmental Biology liver transplantation brain death ALD ischemia-reperfusion growth hormone VEGF |
| title | Relevance of the GH-VEGFB/VEGFA axis in liver grafts from brain-dead donors with alcohol-associated liver disease |
| title_full | Relevance of the GH-VEGFB/VEGFA axis in liver grafts from brain-dead donors with alcohol-associated liver disease |
| title_fullStr | Relevance of the GH-VEGFB/VEGFA axis in liver grafts from brain-dead donors with alcohol-associated liver disease |
| title_full_unstemmed | Relevance of the GH-VEGFB/VEGFA axis in liver grafts from brain-dead donors with alcohol-associated liver disease |
| title_short | Relevance of the GH-VEGFB/VEGFA axis in liver grafts from brain-dead donors with alcohol-associated liver disease |
| title_sort | relevance of the gh vegfb vegfa axis in liver grafts from brain dead donors with alcohol associated liver disease |
| topic | liver transplantation brain death ALD ischemia-reperfusion growth hormone VEGF |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2024.1455258/full |
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