Microarray analysis of gene expression profiles in the rat kidney demonstrates a local inflammatory response induced by cardiopulmonary bypass.
BACKGROUND
Cardiopulmonary bypass (CPB) is a commonly used technique in cardiac surgery but is associated with acute, transient, renal dysfunction that has a negative impact on long-term survival.


OBJECTIVE
To unravel the molecular pathogenesis of renal injury following CPB.


METHODS
To obtain insight into the pathogenesis of renal dysfunction following CPB, we performed a microarray analysis of renal gene expression in the rat.


METHODS
University Medical Centre Groningen.


METHODS
Rats underwent CPB or a sham procedure for 60 min and were sacrificed at 60 min, 1 and 5 days after the procedure.


METHODS
Renal gene expression profile as determined by microarray analysis.


RESULTS
Expression of 420 genes was significantly altered in CPB compared to the sham procedure, and in 407 genes, this was evident in the acute phase (60 min) following CPB. Gene ontology analysis revealed 28 of these genes were involved in inflammatory responses, with high expression of genes downstream of mitogen-activated protein-kinase (MAP-kinase) signalling pathways. Potent inducers identified are from the interleukin-6 cytokine family that consists of interleukin-6 and oncostatin M (OSM), which signal through the gp130-cytokine receptor complex. The plasma concentration of interleukin-6 was hugely increased by CPB as measured by ELISA. Expression of genes downstream of these signalling pathways that lead to production of chemokines, adhesion molecules and molecules involved in coagulative pathways, was upregulated.


CONCLUSIONS
CPB induces an acute and local inflammatory response in the kidney, which might contribute to renal injury. The signalling pathways involved identified by gene expression analysis may represent pharmacological targets to limit renal injury following CPB.
Department of Clinical Pharmacology, University Medical Center Groningen, Groningen, The Netherlands. h.r.bouma@umcg.nl
Hjalmar R
HR
Bouma
Iryna V
IV
Samarska
Maria
M
Schenk
Kilian K K
KK
Dahlem
Hilda
H
van den Bos
Ioan
I
Brebenel
Marry
M
Duin
Martin C
MC
Houwertjes
Bertus G
BG
Loef
Hubert E
HE
Mungroop
Michel M R F
MM
Struys
Anne H
AH
Epema
Robert H
RH
Henning
D000818:Animals; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D007249:Inflammation / Q000473:pathology*; D007668:Kidney / Q000293:injuries / Q000378:metabolism* / Q000503:physiopathology; D020935:MAP Kinase Signaling System; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D013997:Time Factors; D059467:Transcriptome