Gestational intermittent hyperoxia rescues murine genetic congenital heart disease in part

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...

Full description

Saved in:
Bibliographic Details
Published in:Scientific reports 2021-03, Vol.11 (1), p.6608-6608, Article 6608
Main Authors: Doll, Cassandra F., Pereira, Natalia J., Hashimi, Mustafa S., Grindrod, Tabor J., Alkassis, Fariz F., Cai, Lawrence X., Milovanovic, Una, Sandino, Adriana I., Kasahara, Hideko
Format: Article
Language:English
Subjects:
692/4019
692/699
Cardiovascular diseases
Coronary artery disease
Embryos
Genetic diversity
Genetic factors
Genetic variance
Heart diseases
Humanities and Social Sciences
Hyperoxia
multidisciplinary
Mutants
Mutation
Nkx2.5 protein
Science
Science (multidisciplinary)
Ventricle
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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% PO 2 ) 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 (ratio of trabecular layer relative to compact layer area, normoxia 1.84 ± 0.07 vs. hyperoxia 1.51 ± 0.04) and frequency of muscular ventricular septal defects per heart (1.53 ± 0.32 vs. 0.68 ± 0.15); 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.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-021-85569-9