Gene Expression Profiling of Acute Liver Stress During Living Donor Liver Transplantation

During liver transplantation, the donor graft is subjected to a number of acute stresses whose molecular basis is not well‐understood. The effects of surgical stress, preservation and reperfusion injury were studied in 24 consecutive living donor liver transplant (LDLT) operations. Liver biopsies we...

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Veröffentlicht in:American journal of transplantation 2006-04, Vol.6 (4), p.806-824
Hauptverfasser: Borozan, I., Chen, L., Sun, J., Tannis, L. ‐L., Guindi, M., Rotstein, O. D., Heathcote, J., Edwards, A. M., Grant, D., McGilvray, I. D.
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container_end_page 824
container_issue 4
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container_title American journal of transplantation
container_volume 6
creator Borozan, I.
Chen, L.
Sun, J.
Tannis, L. ‐L.
Guindi, M.
Rotstein, O. D.
Heathcote, J.
Edwards, A. M.
Grant, D.
McGilvray, I. D.
description During liver transplantation, the donor graft is subjected to a number of acute stresses whose molecular basis is not well‐understood. The effects of surgical stress, preservation and reperfusion injury were studied in 24 consecutive living donor liver transplant (LDLT) operations. Liver biopsies were taken early in the donor operation (OPENING), after transection of the donor liver (PRECLAMP) and following implantation of the graft (post hepatic artery, [PHA]); these were evaluated for histology, tissue glutathione content and gene expression using a 19K‐human cDNA microarray. LDLT was associated with an ischemia/reperfusion injury, with accumulation of small numbers of neutrophils and decreased glutathione in the PHA biopsies. Following reperfusion, the expression of 129 genes increased and 106 genes decreased when compared to OPENING levels (> or
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LDLT was associated with an ischemia/reperfusion injury, with accumulation of small numbers of neutrophils and decreased glutathione in the PHA biopsies. Following reperfusion, the expression of 129 genes increased and 106 genes decreased when compared to OPENING levels (&gt; or &lt;2‐fold, p &lt; 0.01). By real‐time PCR a subset of 25 genes was verified (15 increased, 10 decreased). These genes were similarly altered in another condition of acute liver stress (the response to braindeath), but not in three chronic liver disease states (HCV, HBV and PBC). This study has identified a set of genes whose expression is altered in acute, but not chronic, liver stress, likely to play a central role in the pathogenesis of acute liver injury of liver transplantation.</description><identifier>ISSN: 1600-6135</identifier><identifier>EISSN: 1600-6143</identifier><identifier>DOI: 10.1111/j.1600-6143.2006.01254.x</identifier><identifier>PMID: 16539639</identifier><language>eng</language><publisher>Oxford UK: Blackwell Publishing Ltd</publisher><subject>Adult ; Biological and medical sciences ; Chronic Disease ; Gene Expression ; Gene Expression Profiling ; Genes ; Hepatitis B virus ; Hepatitis C virus ; Humans ; ischemia/reperfusion ; Liver - metabolism ; Liver - surgery ; Liver Diseases - genetics ; Liver Transplantation ; Living Donors ; Male ; Medical sciences ; Middle Aged ; Oligonucleotide Array Sequence Analysis ; Reperfusion Injury - genetics ; Surgery (general aspects). Transplantations, organ and tissue grafts. 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LDLT was associated with an ischemia/reperfusion injury, with accumulation of small numbers of neutrophils and decreased glutathione in the PHA biopsies. Following reperfusion, the expression of 129 genes increased and 106 genes decreased when compared to OPENING levels (&gt; or &lt;2‐fold, p &lt; 0.01). By real‐time PCR a subset of 25 genes was verified (15 increased, 10 decreased). These genes were similarly altered in another condition of acute liver stress (the response to braindeath), but not in three chronic liver disease states (HCV, HBV and PBC). This study has identified a set of genes whose expression is altered in acute, but not chronic, liver stress, likely to play a central role in the pathogenesis of acute liver injury of liver transplantation.</description><subject>Adult</subject><subject>Biological and medical sciences</subject><subject>Chronic Disease</subject><subject>Gene Expression</subject><subject>Gene Expression Profiling</subject><subject>Genes</subject><subject>Hepatitis B virus</subject><subject>Hepatitis C virus</subject><subject>Humans</subject><subject>ischemia/reperfusion</subject><subject>Liver - metabolism</subject><subject>Liver - surgery</subject><subject>Liver Diseases - genetics</subject><subject>Liver Transplantation</subject><subject>Living Donors</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Oligonucleotide Array Sequence Analysis</subject><subject>Reperfusion Injury - genetics</subject><subject>Surgery (general aspects). 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subjects Adult
Biological and medical sciences
Chronic Disease
Gene Expression
Gene Expression Profiling
Genes
Hepatitis B virus
Hepatitis C virus
Humans
ischemia/reperfusion
Liver - metabolism
Liver - surgery
Liver Diseases - genetics
Liver Transplantation
Living Donors
Male
Medical sciences
Middle Aged
Oligonucleotide Array Sequence Analysis
Reperfusion Injury - genetics
Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases
transplantation
title Gene Expression Profiling of Acute Liver Stress During Living Donor Liver Transplantation
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