The Role of Extracellular-Vesicle-Derived miRNAs in Postoperative Organ Dysfunction in Neonates and Infants...

Despite significant advancements in medical and surgical care, the morbidity and mortality rates of neonates and infants undergoing congenital cardiac surgery remain high. To identify new pathomechanisms associated with postoperative organ dysfunction, extracellular vesicles (EVs) were isolated from plasma from neonates and infants with or without organ dysfunction at three different time points around congenital cardiac surgery, and the EV miRNA expression profiles in the plasma were analyzed. A clear distinction was observed between the organ dysfunction (OD) and non-organ dysfunction (NOD) groups based on their EV miRNA expression profiles. Apoptosis and proinflammatory pathways were consistently upregulated across all time points in the OD group. Complement and coagulation cascades unexpectedly displayed downregulation at the end of the surgery in the OD group, which was verified further at the proteomic level in an independent patient cohort. The neutrophil extracellular trap (NET) formation was enhanced in the OD group across all time points compared to that in the NOD group. As NETs are known to consume complement components, these observed events might be interconnected. A feature selection machine learning method identified miR-200b-5p, miR-4800-5p, miR-363-3p, and miR-483-5p as robustly linked to organ dysfunction following congenital cardiac surgery (accuracy score = 9; SD in accuracy = 0.3162). In conclusion, our study suggested that neonates and infants with postoperative organ dysfunction were associated with enhanced NET formation and complement consumption.