Gestational intermittent hyperoxia rescues murine genetic congenital heart disease in part
Abstract 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. Howeve...
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doaj-497bb0ea0fb842698545a733bc10deff2021-03-28T11:30:28ZengNature Publishing GroupScientific Reports2045-23222021-03-011111910.1038/s41598-021-85569-9Gestational intermittent hyperoxia rescues murine genetic congenital heart disease in partCassandra F. Doll0Natalia J. Pereira1Mustafa S. Hashimi2Tabor J. Grindrod3Fariz F. Alkassis4Lawrence X. Cai5Una Milovanovic6Adriana I. Sandino7Hideko Kasahara8Department of Physiology and Functional Genomics, University of Florida College of MedicineDepartment of Physiology and Functional Genomics, University of Florida College of MedicineDepartment of Physiology and Functional Genomics, University of Florida College of MedicineDepartment of Physiology and Functional Genomics, University of Florida College of MedicineDepartment of Physiology and Functional Genomics, University of Florida College of MedicineDepartment of Physiology and Functional Genomics, University of Florida College of MedicineDepartment of Physiology and Functional Genomics, University of Florida College of MedicineDepartment of Physiology and Functional Genomics, University of Florida College of MedicineDepartment of Physiology and Functional Genomics, University of Florida College of MedicineAbstract 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 (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.https://doi.org/10.1038/s41598-021-85569-9 |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Cassandra F. Doll Natalia J. Pereira Mustafa S. Hashimi Tabor J. Grindrod Fariz F. Alkassis Lawrence X. Cai Una Milovanovic Adriana I. Sandino Hideko Kasahara |
spellingShingle |
Cassandra F. Doll Natalia J. Pereira Mustafa S. Hashimi Tabor J. Grindrod Fariz F. Alkassis Lawrence X. Cai Una Milovanovic Adriana I. Sandino Hideko Kasahara Gestational intermittent hyperoxia rescues murine genetic congenital heart disease in part Scientific Reports |
author_facet |
Cassandra F. Doll Natalia J. Pereira Mustafa S. Hashimi Tabor J. Grindrod Fariz F. Alkassis Lawrence X. Cai Una Milovanovic Adriana I. Sandino Hideko Kasahara |
author_sort |
Cassandra F. Doll |
title |
Gestational intermittent hyperoxia rescues murine genetic congenital heart disease in part |
title_short |
Gestational intermittent hyperoxia rescues murine genetic congenital heart disease in part |
title_full |
Gestational intermittent hyperoxia rescues murine genetic congenital heart disease in part |
title_fullStr |
Gestational intermittent hyperoxia rescues murine genetic congenital heart disease in part |
title_full_unstemmed |
Gestational intermittent hyperoxia rescues murine genetic congenital heart disease in part |
title_sort |
gestational intermittent hyperoxia rescues murine genetic congenital heart disease in part |
publisher |
Nature Publishing Group |
series |
Scientific Reports |
issn |
2045-2322 |
publishDate |
2021-03-01 |
description |
Abstract 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 (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. |
url |
https://doi.org/10.1038/s41598-021-85569-9 |
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