| Autor: |
Hsieh L; Department of Pediatrics (Cardiology) University of Washington Seattle WA.; Center for Developmental Biology and Regenerative Medicine Seattle Children's Research Institute Seattle WA., Tu LN; Department of Pediatrics (Cardiology) University of Washington Seattle WA.; Center for Developmental Biology and Regenerative Medicine Seattle Children's Research Institute Seattle WA., Paquette A; Center for Developmental Biology and Regenerative Medicine Seattle Children's Research Institute Seattle WA., Sheng Q; Department of Biostatistics Vanderbilt University Medical Center Nashville TN., Zhao S; Department of Biostatistics Vanderbilt University Medical Center Nashville TN., Bittel D; Ward Family Heart Center Children's Mercy Hospital Kansas City MO.; College of Biosciences Kansas City University of Medicine and Biosciences Kansas City MO., O'Brien J; Ward Family Heart Center Children's Mercy Hospital Kansas City MO., Vickers K; Department of Medicine Vanderbilt University Medical Center Nashville TN., Pastuszko P; Department of Cardiovascular Surgery Icahn School of Medicine at Mount Sinai New York NY., Nigam V; Department of Pediatrics (Cardiology) University of Washington Seattle WA.; Center for Developmental Biology and Regenerative Medicine Seattle Children's Research Institute Seattle WA. |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of the American Heart Association [J Am Heart Assoc] 2022 Sep 06; Vol. 11 (17), pp. e025864. Date of Electronic Publication: 2022 Aug 24. |
| DOI: |
10.1161/JAHA.122.025864 |
| Abstrakt: |
Background The systemic inflammation that occurs after exposure to cardiopulmonary bypass (CPB), which is especially severe in neonatal patients, is associated with poorer outcomes and is not well understood. In order to gain deeper insight into how exposure to bypass activates inflammatory responses in circulating leukocytes, we studied changes in microRNA (miRNA) expression during and after exposure to bypass. miRNAs are small noncoding RNAs that have important roles in modulating protein levels and function of cells. Methods and Results We performed miRNA-sequencing on leukocytes isolated from neonatal patients with CPB (n=5) at 7 time points during the process of CPB, including before the initiation of bypass, during bypass, and at 3 time points during the first 24 hours after weaning from bypass. We identified significant differentially expressed miRNAs using generalized linear regression models, and miRNAs were defined as statistically significant using a false discovery rate-adjusted P <0.05. We identified gene targets of these miRNAs using the TargetScan database and identified significantly enriched biological pathways for these gene targets. We identified 54 miRNAs with differential expression during and after CPB. These miRNAs clustered into 3 groups, including miRNAs that were increased during and after CPB (3 miRNAs), miRNAs that decreased during and after CPB (10 miRNAs), and miRNAs that decreased during CPB but then increased 8 to 24 hours after CPB. A total of 38.9% of the target genes of these miRNAs were significantly differentially expressed in our previous study. miRNAs with altered expression levels are predicted to significantly modulate pathways related to inflammation and signal transduction. Conclusions The unbiased profiling of the miRNA changes that occur in the circulating leukocytes of patients with bypass provides deeper insight into the mechanisms that underpin the systemic inflammatory response that occurs in patients after exposure to CPB. These data will help the development of novel treatments and biomarkers for bypass-associated inflammation. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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