RT Journal Article SR Electronic T1 Neonatal hyperoxia inhibits proliferation of atrial cardiomyocytes by suppressing fatty acid synthesis JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.06.01.127621 DO 10.1101/2020.06.01.127621 A1 Ethan David Cohen A1 Min Yee A1 George A. Porter, Jr. A1 Andrew N. McDavid A1 Paul S. Brookes A1 Gloria S. Pryhuber A1 Michael A. O’Reilly YR 2020 UL http://biorxiv.org/content/early/2020/06/02/2020.06.01.127621.abstract AB 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 inhibits the proliferation of left atrial cardiomyocytes and causes diastolic heart failure by thinning the walls of the left atrium and disrupting its ability to pump effectively. 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 while overexpressing these genes maintained their expansion in hyperoxic conditions, suggesting hyperoxia directly inhibits atrial cardiomyocyte proliferation 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.Competing Interest StatementThe authors have declared no competing interest.