microRNA Expression Levels Change in Neonatal Patients During and After Exposure to Cardiopulmonary Bypass
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 response...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2022-09-01
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| Series: | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| Subjects: | |
| Online Access: | https://www.ahajournals.org/doi/10.1161/JAHA.122.025864 |
| _version_ | 1828379172996644864 |
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| author | Lance Hsieh Lan N. Tu Alison Paquette Quanhu Sheng Shilin Zhao Douglas Bittel James O’Brien Kasey Vickers Peter Pastuszko Vishal Nigam |
| author_facet | Lance Hsieh Lan N. Tu Alison Paquette Quanhu Sheng Shilin Zhao Douglas Bittel James O’Brien Kasey Vickers Peter Pastuszko Vishal Nigam |
| author_sort | Lance Hsieh |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-10T03:35:55Z |
| format | Article |
| id | doaj.art-3cec4c77430c4f409061127ace36ec7c |
| institution | Directory Open Access Journal |
| issn | 2047-9980 |
| language | English |
| last_indexed | 2024-12-10T03:35:55Z |
| publishDate | 2022-09-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| spelling | doaj.art-3cec4c77430c4f409061127ace36ec7c2022-12-22T02:03:42ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802022-09-01111710.1161/JAHA.122.025864microRNA Expression Levels Change in Neonatal Patients During and After Exposure to Cardiopulmonary BypassLance Hsieh0Lan N. Tu1Alison Paquette2Quanhu Sheng3Shilin Zhao4Douglas Bittel5James O’Brien6Kasey Vickers7Peter Pastuszko8Vishal Nigam9Department of Pediatrics (Cardiology) University of Washington Seattle WADepartment of Pediatrics (Cardiology) University of Washington Seattle WACenter for Developmental Biology and Regenerative Medicine Seattle Children’s Research Institute Seattle WADepartment of Biostatistics Vanderbilt University Medical Center Nashville TNDepartment of Biostatistics Vanderbilt University Medical Center Nashville TNWard Family Heart Center Children’s Mercy Hospital Kansas City MOWard Family Heart Center Children’s Mercy Hospital Kansas City MODepartment of Medicine Vanderbilt University Medical Center Nashville TNDepartment of Cardiovascular Surgery Icahn School of Medicine at Mount Sinai New York NYDepartment of Pediatrics (Cardiology) University of Washington Seattle WABackground 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.https://www.ahajournals.org/doi/10.1161/JAHA.122.025864cardiopulmonary bypassinflammationmicroRNAneonate |
| spellingShingle | Lance Hsieh Lan N. Tu Alison Paquette Quanhu Sheng Shilin Zhao Douglas Bittel James O’Brien Kasey Vickers Peter Pastuszko Vishal Nigam microRNA Expression Levels Change in Neonatal Patients During and After Exposure to Cardiopulmonary Bypass Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease cardiopulmonary bypass inflammation microRNA neonate |
| title | microRNA Expression Levels Change in Neonatal Patients During and After Exposure to Cardiopulmonary Bypass |
| title_full | microRNA Expression Levels Change in Neonatal Patients During and After Exposure to Cardiopulmonary Bypass |
| title_fullStr | microRNA Expression Levels Change in Neonatal Patients During and After Exposure to Cardiopulmonary Bypass |
| title_full_unstemmed | microRNA Expression Levels Change in Neonatal Patients During and After Exposure to Cardiopulmonary Bypass |
| title_short | microRNA Expression Levels Change in Neonatal Patients During and After Exposure to Cardiopulmonary Bypass |
| title_sort | microrna expression levels change in neonatal patients during and after exposure to cardiopulmonary bypass |
| topic | cardiopulmonary bypass inflammation microRNA neonate |
| url | https://www.ahajournals.org/doi/10.1161/JAHA.122.025864 |
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