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ResearchIn-Press PreviewCardiology Open Access | 10.1172/jci.insight.140785

Neonatal hyperoxia inhibits proliferation and survival of atrial cardiomyocytes by suppressing fatty acid synthesis

Ethan David Cohen,1 Min Yee,1 George A. Porter, Jr.,1 Erin E. Ritzer,1 Andrew N. McDavid,2 Paul S. Brookes,3 Gloria S. Pryhuber,1 and Michael A. O'Reilly1

1Department of Pediatrics, The University of Rochester, Rochester, United States of America

2Department of Statistics and Computational Biology, The University of Rochester, Rochester, United States of America

3Department of Anesthesiology, The University of Rochester, Rochester, United States of America

Find articles by Cohen, E. in: JCI | PubMed | Google Scholar

1Department of Pediatrics, The University of Rochester, Rochester, United States of America

2Department of Statistics and Computational Biology, The University of Rochester, Rochester, United States of America

3Department of Anesthesiology, The University of Rochester, Rochester, United States of America

Find articles by Yee, M. in: JCI | PubMed | Google Scholar

1Department of Pediatrics, The University of Rochester, Rochester, United States of America

2Department of Statistics and Computational Biology, The University of Rochester, Rochester, United States of America

3Department of Anesthesiology, The University of Rochester, Rochester, United States of America

Find articles by Porter, Jr., G. in: JCI | PubMed | Google Scholar |

1Department of Pediatrics, The University of Rochester, Rochester, United States of America

2Department of Statistics and Computational Biology, The University of Rochester, Rochester, United States of America

3Department of Anesthesiology, The University of Rochester, Rochester, United States of America

Find articles by Ritzer, E. in: JCI | PubMed | Google Scholar

1Department of Pediatrics, The University of Rochester, Rochester, United States of America

2Department of Statistics and Computational Biology, The University of Rochester, Rochester, United States of America

3Department of Anesthesiology, The University of Rochester, Rochester, United States of America

Find articles by McDavid, A. in: JCI | PubMed | Google Scholar |

1Department of Pediatrics, The University of Rochester, Rochester, United States of America

2Department of Statistics and Computational Biology, The University of Rochester, Rochester, United States of America

3Department of Anesthesiology, The University of Rochester, Rochester, United States of America

Find articles by Brookes, P. in: JCI | PubMed | Google Scholar |

1Department of Pediatrics, The University of Rochester, Rochester, United States of America

2Department of Statistics and Computational Biology, The University of Rochester, Rochester, United States of America

3Department of Anesthesiology, The University of Rochester, Rochester, United States of America

Find articles by Pryhuber, G. in: JCI | PubMed | Google Scholar

1Department of Pediatrics, The University of Rochester, Rochester, United States of America

2Department of Statistics and Computational Biology, The University of Rochester, Rochester, United States of America

3Department of Anesthesiology, The University of Rochester, Rochester, United States of America

Find articles by O'Reilly, M. in: JCI | PubMed | Google Scholar |

Published January 28, 2021 - More info

JCI Insight. https://doi.org/10.1172/jci.insight.140785.
Copyright © 2021, Cohen et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published January 28, 2021 - Version history
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Abstract

Preterm birth increases the risk for pulmonary hypertension and heart failure in adulthood. Oxygen therapy can damage the immature cardiopulmonary system and may be partially responsible for the cardiovascular disease in adults born preterm. We previously showed that exposing newborn mice to hyperoxia causes pulmonary hypertension by 1 year of age that is preceded by a poorly understood loss of pulmonary vein cardiomyocyte proliferation. We now show that hyperoxia also reduces cardiomyocyte proliferation and survival in the left atrium and causes diastolic heart failure by disrupting its filling of the left ventricle. Transcriptomic profiling showed that neonatal hyperoxia permanently suppressed fatty acid synthase (Fasn), stearoyl-CoA desaturase 1 (Scd1) and other fatty acid synthesis genes in the atria of mice, the HL-1 line of mouse atrial cardiomyocytes and left atrial tissue explanted from human infants. Suppressing Fasn or Scd1 reduced HL-1 cell proliferation and increased cell death while overexpressing these genes maintained their expansion in hyperoxia, suggesting oxygen directly inhibits atrial cardiomyocyte proliferation and survival by repressing Fasn and Scd1. Pharmacologic interventions that restore Fasn, Scd1 and other fatty acid synthesis genes in atrial cardiomyocytes may thus provide a way of ameliorating the adverse effects of supplemental oxygen on preterm infants.

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