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Abrogation of graft ischemia‐reperfusion injury in ischemia‐free liver transplantation
BACKGROUND: Ischemia‐reperfusion injury (IRI) is considered an inherent component of organ transplantation that compromises transplant outcomes and organ availability. The ischemia‐free liver transplantation (IFLT) procedure has been developed to avoid interruption of blood supply to liver grafts. I...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9042797/ https://www.ncbi.nlm.nih.gov/pubmed/35474299 http://dx.doi.org/10.1002/ctm2.546 |
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author | Guo, Zhiyong Xu, Jinghong Huang, Shanzhou Yin, Meixian Zhao, Qiang Ju, Weiqiang Wang, Dongping Gao, Ningxin Huang, Changjun Yang, Lu Chen, Maogen Zhang, Zhiheng Zhu, Zebin Wang, Linhe Zhu, Caihui Zhang, Yixi Tang, Yunhua Chen, Haitian Liu, Kunpeng Lu, Yuting Ma, Yi Hu, Anbin Chen, Yinghua Zhu, Xiaofeng He, Xiaoshun |
author_facet | Guo, Zhiyong Xu, Jinghong Huang, Shanzhou Yin, Meixian Zhao, Qiang Ju, Weiqiang Wang, Dongping Gao, Ningxin Huang, Changjun Yang, Lu Chen, Maogen Zhang, Zhiheng Zhu, Zebin Wang, Linhe Zhu, Caihui Zhang, Yixi Tang, Yunhua Chen, Haitian Liu, Kunpeng Lu, Yuting Ma, Yi Hu, Anbin Chen, Yinghua Zhu, Xiaofeng He, Xiaoshun |
author_sort | Guo, Zhiyong |
collection | PubMed |
description | BACKGROUND: Ischemia‐reperfusion injury (IRI) is considered an inherent component of organ transplantation that compromises transplant outcomes and organ availability. The ischemia‐free liver transplantation (IFLT) procedure has been developed to avoid interruption of blood supply to liver grafts. It is unknown how IFLT might change the characteristics of graft IRI. METHODS: Serum and liver biopsy samples were collected from IFLT and conventional liver transplantation (CLT) recipients. Pathological, metabolomics, transcriptomics, and proteomics analyses were performed to identify the characteristic changes in graft IRI in IFLT. RESULTS: Peak aspartate aminotransferase (539.59 ± 661.76 U/L versus 2622.28 ± 3291.57 U/L) and alanine aminotransferase (297.64 ± 549.50 U/L versus 1184.16 ± 1502.76 U/L) levels within the first 7 days and total bilirubin levels by day 7 (3.27 ± 2.82 mg/dl versus 8.33 ± 8.76 mg/dl) were lower in the IFLT versus CLT group (all p values < 0.001). The pathological characteristics of IRI were more obvious in CLT grafts. The antioxidant pentose phosphate pathway remained active throughout the procedure in IFLT grafts and was suppressed during preservation and overactivated postrevascularization in CLT grafts. Gene transcriptional reprogramming was almost absent during IFLT but was profound during CLT. Proteomics analysis showed that “metabolism of RNA” was the major differentially expressed process between the two groups. Several proinflammatory pathways were not activated post‐IFLT as they were post‐CLT. The activities of natural killer cells, macrophages, and neutrophils were lower in IFLT grafts than in CLT grafts. The serum levels of 14 cytokines were increased in CLT versus IFLT recipients. CONCLUSIONS: IFLT can largely avoid the biological consequences of graft IRI, thus has the potential to improve transplant outcome while increasing organ utilization. |
format | Online Article Text |
id | pubmed-9042797 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-90427972022-04-28 Abrogation of graft ischemia‐reperfusion injury in ischemia‐free liver transplantation Guo, Zhiyong Xu, Jinghong Huang, Shanzhou Yin, Meixian Zhao, Qiang Ju, Weiqiang Wang, Dongping Gao, Ningxin Huang, Changjun Yang, Lu Chen, Maogen Zhang, Zhiheng Zhu, Zebin Wang, Linhe Zhu, Caihui Zhang, Yixi Tang, Yunhua Chen, Haitian Liu, Kunpeng Lu, Yuting Ma, Yi Hu, Anbin Chen, Yinghua Zhu, Xiaofeng He, Xiaoshun Clin Transl Med Research Articles BACKGROUND: Ischemia‐reperfusion injury (IRI) is considered an inherent component of organ transplantation that compromises transplant outcomes and organ availability. The ischemia‐free liver transplantation (IFLT) procedure has been developed to avoid interruption of blood supply to liver grafts. It is unknown how IFLT might change the characteristics of graft IRI. METHODS: Serum and liver biopsy samples were collected from IFLT and conventional liver transplantation (CLT) recipients. Pathological, metabolomics, transcriptomics, and proteomics analyses were performed to identify the characteristic changes in graft IRI in IFLT. RESULTS: Peak aspartate aminotransferase (539.59 ± 661.76 U/L versus 2622.28 ± 3291.57 U/L) and alanine aminotransferase (297.64 ± 549.50 U/L versus 1184.16 ± 1502.76 U/L) levels within the first 7 days and total bilirubin levels by day 7 (3.27 ± 2.82 mg/dl versus 8.33 ± 8.76 mg/dl) were lower in the IFLT versus CLT group (all p values < 0.001). The pathological characteristics of IRI were more obvious in CLT grafts. The antioxidant pentose phosphate pathway remained active throughout the procedure in IFLT grafts and was suppressed during preservation and overactivated postrevascularization in CLT grafts. Gene transcriptional reprogramming was almost absent during IFLT but was profound during CLT. Proteomics analysis showed that “metabolism of RNA” was the major differentially expressed process between the two groups. Several proinflammatory pathways were not activated post‐IFLT as they were post‐CLT. The activities of natural killer cells, macrophages, and neutrophils were lower in IFLT grafts than in CLT grafts. The serum levels of 14 cytokines were increased in CLT versus IFLT recipients. CONCLUSIONS: IFLT can largely avoid the biological consequences of graft IRI, thus has the potential to improve transplant outcome while increasing organ utilization. John Wiley and Sons Inc. 2022-04-26 /pmc/articles/PMC9042797/ /pubmed/35474299 http://dx.doi.org/10.1002/ctm2.546 Text en © 2021 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles Guo, Zhiyong Xu, Jinghong Huang, Shanzhou Yin, Meixian Zhao, Qiang Ju, Weiqiang Wang, Dongping Gao, Ningxin Huang, Changjun Yang, Lu Chen, Maogen Zhang, Zhiheng Zhu, Zebin Wang, Linhe Zhu, Caihui Zhang, Yixi Tang, Yunhua Chen, Haitian Liu, Kunpeng Lu, Yuting Ma, Yi Hu, Anbin Chen, Yinghua Zhu, Xiaofeng He, Xiaoshun Abrogation of graft ischemia‐reperfusion injury in ischemia‐free liver transplantation |
title | Abrogation of graft ischemia‐reperfusion injury in ischemia‐free liver transplantation |
title_full | Abrogation of graft ischemia‐reperfusion injury in ischemia‐free liver transplantation |
title_fullStr | Abrogation of graft ischemia‐reperfusion injury in ischemia‐free liver transplantation |
title_full_unstemmed | Abrogation of graft ischemia‐reperfusion injury in ischemia‐free liver transplantation |
title_short | Abrogation of graft ischemia‐reperfusion injury in ischemia‐free liver transplantation |
title_sort | abrogation of graft ischemia‐reperfusion injury in ischemia‐free liver transplantation |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9042797/ https://www.ncbi.nlm.nih.gov/pubmed/35474299 http://dx.doi.org/10.1002/ctm2.546 |
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