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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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/497bb0ea0fb842698545a733bc10deff
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spelling	oai:doaj.org-article:497bb0ea0fb842698545a733bc10deff2021-12-02T16:36:12ZGestational intermittent hyperoxia rescues murine genetic congenital heart disease in part10.1038/s41598-021-85569-92045-2322https://doaj.org/article/497bb0ea0fb842698545a733bc10deff2021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-85569-9https://doaj.org/toc/2045-2322Abstract 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.Cassandra F. DollNatalia J. PereiraMustafa S. HashimiTabor J. GrindrodFariz F. AlkassisLawrence X. CaiUna MilovanovicAdriana I. SandinoHideko KasaharaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q 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
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.
format	article
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
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 Portfolio
publishDate	2021
url	https://doaj.org/article/497bb0ea0fb842698545a733bc10deff
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Gestational intermittent hyperoxia rescues murine genetic congenital heart disease in part

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