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Effect of ischemic preconditioning on the genomic response to reperfusion injury in deceased donor liver transplantation
Author(s) -
Jassem Wayel,
Fuggle Susan,
Thompson Richard,
Arno Matthew,
Taylor Jennifer,
Byrne Jane,
Heaton Nigel,
Rela Mohamed
Publication year - 2009
Publication title -
liver transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.814
H-Index - 150
eISSN - 1527-6473
pISSN - 1527-6465
DOI - 10.1002/lt.21936
Subject(s) - reperfusion injury , liver transplantation , medicine , microarray , transplantation , gene expression , ischemic preconditioning , real time polymerase chain reaction , gene chip analysis , microarray analysis techniques , immune system , gene , cancer research , andrology , immunology , ischemia , biology , biochemistry
Ischemic preconditioning (IP) is an effective method for protecting organs from ischemia/reperfusion (IR) injury; however, the molecular basis of this protective effect is poorly understood. This study assessed the gene expression profile in liver allografts during transplantation and evaluated the impact of IP. Prereperfusion and postreperfusion biopsy specimens from livers subjected to IP (n = 19) or no preconditioning (the IR group; n = 16) were obtained. Total RNA was extracted and hybridized to GeneChip microarrays, and the findings were validated with real‐time quantitative reverse‐transcription polymerase chain reaction (qRT‐PCR). IP livers showed less of an increase in aspartate aminotransferase after transplantation. A microarray analysis of the IR group showed increased expression of 57 genes mainly involved in cell death, inflammation and immune response, stress, and modulation of the cell cycle. The IP group showed attenuation of the expression of these genes after reperfusion. Additionally, IP led to increased expression of 43 genes involved in growth and maintenance, cell‐cycle regulation, proliferation, and development. The expression of the 12 most significant genes was validated in all patients with real‐time qRT‐PCR, and the fold changes of a number of genes correlated with clinical parameters and graft outcomes. IP protection of liver allografts was associated with a reduction in the expression of immune response genes and promotion of those involved in protection and repair. Liver Transpl 15:1750–1765, 2009. © 2009 AASLD.