Effect of ischemic preconditioning on the genomic response to reperfusion injury in deceased donor liver transplantation.
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.
Jassem
Wayel
W
Liver Transplant Unit, Institute of Liver Studies, King's College Hospital, London, United Kingdom.
Fuggle
Susan
S
Thompson
Richard
R
Arno
Matthew
M
Taylor
Jennifer
J
Byrne
Jane
J
Heaton
Nigel
N
Rela
Mohamed
M
D000208:Acute Disease; D000328:Adult; D001706:Biopsy; D050377:Cold Ischemia; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D006084:Graft Rejection / Q000235:genetics* / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D006801:Humans; D019194:Ischemic Preconditioning; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000378:metabolism; D015427:Reperfusion Injury / Q000235:genetics* / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014158:Transcription, Genetic; D014184:Transplantation, Homologous; D016896:Treatment Outcome
D012333:RNA, Messenger