Cardiac Left Ventricle Mitochondrial Dysfunction After Neonatal Exposure to Hyperoxia: Relevance for Cardiomyopathy After Preterm Birth.

Hypertension

Department of Pediatrics, Sainte-Justine University Hospital (Centre Hospitalier Universitaire Sainte-Justine) and Research Centre (D.R.D., A.F., C.N.R.P., Y.H., A.D., A.C., G.C., P.G., J.-L.B., J.-S.J., T.M.L., A.M.N.), Faculty of Medicine, University of Montreal, Quebec, Canada.

Published: March 2022

AI Article Synopsis

  • Individuals born preterm show changes in the left ventricle and have a higher risk of heart diseases, and this study explores how neonatal hyperoxia (high oxygen exposure) affects left ventricle mitochondria in rats, simulating preterm birth conditions.
  • The research found that rats exposed to high oxygen had smaller mitochondria, impaired function, and signs of oxidative stress, indicating potential cardiac issues.
  • In human young adults, those born preterm had lower levels of a mitochondrial peptide called humanin, which correlated with specific heart function metrics, suggesting lasting impacts of preterm birth on heart health.

Article Abstract

Background: Individuals born preterm present left ventricle changes and increased risk of cardiac diseases and heart failure. The pathophysiology of heart disease after preterm birth is incompletely understood. Mitochondria dysfunction is a hallmark of cardiomyopathy resulting in heart failure. We hypothesized that neonatal hyperoxia in rats, a recognized model simulating preterm birth conditions and resulting in oxygen-induced cardiomyopathy, induce left ventricle mitochondrial changes in juvenile rats. We also hypothesized that humanin, a mitochondrial-derived peptide, would be reduced in young adults born preterm.

Methods: Sprague-Dawley pups were exposed to room air (controls) or 80% O at postnatal days 3 to 10 (oxygen-induced cardiomyopathy). We studied left ventricle mitochondrial changes in 4 weeks old males. In a cohort of young adults born preterm (n=55) and age-matched term (n=54), we compared circulating levels of humanin.

Results: Compared with controls, oxygen-exposed rats showed smaller left ventricle mitochondria with disrupted integrity on electron microscopy, decreased oxidative phosphorylation, increased glycolysis markers, and reduced mitochondrial biogenesis and abundance. In oxygen-exposed rats, we observed lipid deposits, increased superoxide production (isolated cardiomyocytes), and reduced gene expression. In the cohort, left ventricle ejection fraction and peak global longitudinal strain were similar between groups however humanin levels were lower in preterm and associated with left ventricle ejection fraction and peak global longitudinal strain.

Conclusions: In conclusion, neonatal hyperoxia impaired left ventricle mitochondrial structure and function in juvenile animals. Serum humanin level was reduced in preterm adults. This study suggests that preterm birth-related conditions entail left ventricle mitochondrial alterations that may underlie cardiac changes perpetuated into adulthood. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03261609.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8823906PMC
http://dx.doi.org/10.1161/HYPERTENSIONAHA.121.17979DOI Listing

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