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Cardiopulmonary bypass changes the plasma proteome in children undergoing tetralogy of Fallot repair
M Hepponstall1, V Ignjatovic2, S Binos3
1Murdoch Childrens Research Institute, Melbourne, Australia Cardiac Surgery Unit, Royal Children's Hospital, Melbourne, Australia Department of Paediatrics, The University of Melbourne, Melbourne, Australia Department of Primary Industries, Bioscience Research Division, Melbourne, Australia.
Insights
Cardiopulmonary bypass (CPB) significantly alters the plasma proteome in children undergoing tetralogy of Fallot repair, with changes most evident 6-12 hours post-procedure. Protein levels returned to baseline within 24 hours.
Area of Science:
- Biochemistry
- Proteomics
- Pediatric Cardiology
Background:
- Cardiopulmonary bypass (CPB) is linked to adverse clinical outcomes.
- The precise effects of CPB on inflammatory, immunological, and homeostatic pathways are not fully understood.
- Investigating CPB's impact on the plasma proteome is crucial for understanding its systemic effects.
Purpose of the Study:
- To investigate the impact of CPB on the plasma proteome in pediatric patients.
- To identify specific proteins affected by CPB during tetralogy of Fallot repair.
Main Methods:
- Plasma samples collected from 20 children before, during, and at 6, 12, and 24 hours after CPB.
- Liquid chromatography-mass spectrometry (LC-MS) used for label-free, untargeted plasma proteome analysis.
- Differential protein expression identified using Genedata software with a p<0.01 threshold and false discovery rate control.
Main Results:
- Seven proteins demonstrated differential expression post-CPB: haptoglobin isoform 1 preproprotein, semaphorin-6C isoform 2, vitamin D-binding protein, inter-alpha-trypsin inhibitor, ceruloplasmin, apolipoprotein B100, and fibrinogen alpha.
- Plasma proteome alterations were most pronounced at 6 and 12 hours after CPB.
- No proteins remained differentially regulated by the 24-hour time point.
Conclusions:
- CPB induces significant, yet transient, changes in the plasma proteome of children undergoing tetralogy of Fallot repair.
- The proteomic profile largely returns to baseline within 24 hours post-CPB.
- These findings contribute to understanding the systemic homeostatic response to CPB in pediatric cardiac surgery.
Introduction:
Cardiopulmonary bypass (CPB) can be associated with deleterious clinical effects. However, the impact of CPB on inflammatory, immunological and other homeostatic pathways remains poorly understood. We investigated the impact of CPB on the plasma proteome in children undergoing tetralogy of Fallot repair.
Methods:
Blood samples were taken from 20 children prior to and at the end of CPB and 6h, 12h and 24h after CPB. Plasma was analysed by liquid chromatography-mass spectrometry (LC-MS) in a label-free, untargeted approach. Data were analysed using Genedata software to identify peptides that were differentially expressed (p<0.01 above a false discovery rate). Proteins were identified from peptides that demonstrated differential expression.
Results:
The proteins that were found to be differentially expressed were haptoglobin isoform 1 preproprotein, isoform 2 of semaphorin-6C, vitamin D-binding protein, inter-alpha-trypsin inhibitor, ceruloplasmin, apolipoprotein B100 and fibrinogen alpha.
Conclusion:
CPB alters the plasma proteome with differences most apparent at 6h and 12h post CPB. There was a return to baseline with no proteins differentially regulated by 24h.
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