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Cassandra F. Doll (1), Natalia J. Pereira (1), Mustafa S. Hashimi (1), Tabor J. Grindrod (1), Fariz F. Alkassis (1), Lawrence X. Cai (1), Una Milovanovic (1), Adriana I. Sandino (1), Hideko Kasahara (1,2)
Scientific Reports, 11, Issue 6608, March 2021. DOI: 10.1038/s41598-021-85569-9
Cardiac development is a dynamic process, temporally and spatially. When disturbed, it leads to congenital cardiac anomalies that affect approximately 1% of live births. Genetic variants in several loci lead to anomalies, with the transcription factor NKX2-5 being one of the largest. However, there are also non-genetic factors that influence cardiac malformations. We examined the hypothesis that hyperoxia may be beneficial and can rescue genetic cardiac anomalies induced by an Nkx2-5 mutation. Intermittent mild hyperoxia (40% PO2) was applied for 10 h per day to normal wild-type female mice mated with heterozygous Nkx2-5 mutant males from gestational day 8.5 to birth. Hyperoxia therapy reduced excessive trabeculation in Nkx2-5 mutant mice compared to normoxic conditions; however, the incidence of membranous ventricular septal defects in Nkx2-5 mutant hearts was not changed. Nkx2-5 mutant embryonic hearts showed defective coronary vessel organization, which was improved by intermittent mild hyperoxia. The results of our study showed that mild gestational hyperoxia therapy rescued genetic cardiac malformation induced by Nkx2-5 mutation in part.
Dragonfly was used to generate and analyze 3D X-ray images of neonatal mouse hearts.
(1) Department of Physiology and Functional Genomics, University of Florida College of Medicine, 1600 SW Archer Rd. M543, Gainesville, FL 32610‑0274, USA.
(2) International University of Health and Welfare, School of Medicine, 852 Hatakeda, Narita, Chiba, Japan.
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