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

JCI Insight. 2021 Mar 8;6(5):e140785. doi: 10.1172/jci.insight.140785.


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 that 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.

Keywords: Cardiology; Cardiovascular disease; Fatty acid oxidation; Mouse models.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Cell Death
  • Cell Proliferation
  • Disease Models, Animal
  • Fatty Acid Synthases / antagonists & inhibitors
  • Fatty Acid Synthases / metabolism*
  • Fatty Acids / biosynthesis*
  • Female
  • Heart Atria / cytology*
  • Heart Atria / pathology
  • Humans
  • Hyperoxia
  • Infant, Newborn
  • Infant, Premature
  • Lipogenesis
  • Male
  • Mice, Inbred C57BL
  • Myocytes, Cardiac / metabolism*
  • Myocytes, Cardiac / pathology
  • Oxygen / administration & dosage
  • Oxygen / adverse effects*
  • Premature Birth*
  • Respiratory Therapy
  • Stearoyl-CoA Desaturase / antagonists & inhibitors
  • Stearoyl-CoA Desaturase / metabolism*
  • Transcriptome


  • Fatty Acids
  • Stearoyl-CoA Desaturase
  • Fatty Acid Synthases
  • Oxygen