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Vulnerability of the developing heart to oxygen deprivation as a cause of congenital heart defects.

Kenchegowda D, Liu H, Thompson K, Luo L, Martin SS, Fisher SA - J Am Heart Assoc (2014)

Bottom Line: The heart develops under reduced and varying oxygen concentrations, yet there is little understanding of oxygen metabolism in the normal and mal-development of the heart.ODD-Luc activity decreased in 2 stages, the first corresponding with the formation of a functional cardiovascular system for oxygen delivery at E15.5, and the second after birth consistent with complete oxygenation of the blood and tissues.Low oxygen concentrations and lack of oxygen reserve during a critical phase of heart organogenesis may provide a basis for vulnerability to the development of common septation and conotruncal heart defects.

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiovascular Medicine, University of Maryland School of Medicine, Baltimore, MD (D.K., S.A.F.).

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Related in: MedlinePlus

NCC fate map in an E15.5 embryo with Wnt1Cre mediated inactivation of Hif‐1α. NCC fate is mapped with histological detection of LacZ activity from the Rosa26 locus. Matched sections are from anterior to posterior. In control (A and B; Hif‐1αf/f; Wnt1Cre−) and cKO (C and D; Hif‐1αf/f; Wnt1Cre+) embryos, LacZ+ cells are present in the aorta, pulmonary artery and the semilunar valves. In the control embryo LacZ+ cells are evident in the rostral portion of the ventricular septum below the aortic valve (B). The outlet septum is absent in the cKO accounting for the outlet VSD. D, LacZ+ cells are observed in cKO in the abnormally positioned aortico‐pulmonic septum (arrow), which is incomplete resulting in PTA. Scale bars: 500 μm. Ao indicates aorta; cKO, conditional knock‐out; Hif, hypoxia‐inducible transcription factor; NCC, neural crest cells; pa, pulmonary artery; PTA, persistent truncus arteriosus; VSD, ventricular septal defect.
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fig06: NCC fate map in an E15.5 embryo with Wnt1Cre mediated inactivation of Hif‐1α. NCC fate is mapped with histological detection of LacZ activity from the Rosa26 locus. Matched sections are from anterior to posterior. In control (A and B; Hif‐1αf/f; Wnt1Cre−) and cKO (C and D; Hif‐1αf/f; Wnt1Cre+) embryos, LacZ+ cells are present in the aorta, pulmonary artery and the semilunar valves. In the control embryo LacZ+ cells are evident in the rostral portion of the ventricular septum below the aortic valve (B). The outlet septum is absent in the cKO accounting for the outlet VSD. D, LacZ+ cells are observed in cKO in the abnormally positioned aortico‐pulmonic septum (arrow), which is incomplete resulting in PTA. Scale bars: 500 μm. Ao indicates aorta; cKO, conditional knock‐out; Hif, hypoxia‐inducible transcription factor; NCC, neural crest cells; pa, pulmonary artery; PTA, persistent truncus arteriosus; VSD, ventricular septal defect.

Mentions: Hif‐1αf/f mice were crossed with Rosa26‐LacZ mice to fate map NCCs migrating into the OFT using LacZ staining. In a Hif‐1αf/f; Wnt1Cre+ embryo with PTA, LacZ+ cells populate the great vessels and OFT, including the defective aortic‐pulmonic septum (Figures 6C and 6D; compare to control 6A and 6B). This suggests that HIF‐1α is not required within the NCCs for their migration into the cardiac OFT.


Vulnerability of the developing heart to oxygen deprivation as a cause of congenital heart defects.

Kenchegowda D, Liu H, Thompson K, Luo L, Martin SS, Fisher SA - J Am Heart Assoc (2014)

NCC fate map in an E15.5 embryo with Wnt1Cre mediated inactivation of Hif‐1α. NCC fate is mapped with histological detection of LacZ activity from the Rosa26 locus. Matched sections are from anterior to posterior. In control (A and B; Hif‐1αf/f; Wnt1Cre−) and cKO (C and D; Hif‐1αf/f; Wnt1Cre+) embryos, LacZ+ cells are present in the aorta, pulmonary artery and the semilunar valves. In the control embryo LacZ+ cells are evident in the rostral portion of the ventricular septum below the aortic valve (B). The outlet septum is absent in the cKO accounting for the outlet VSD. D, LacZ+ cells are observed in cKO in the abnormally positioned aortico‐pulmonic septum (arrow), which is incomplete resulting in PTA. Scale bars: 500 μm. Ao indicates aorta; cKO, conditional knock‐out; Hif, hypoxia‐inducible transcription factor; NCC, neural crest cells; pa, pulmonary artery; PTA, persistent truncus arteriosus; VSD, ventricular septal defect.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4309110&req=5

fig06: NCC fate map in an E15.5 embryo with Wnt1Cre mediated inactivation of Hif‐1α. NCC fate is mapped with histological detection of LacZ activity from the Rosa26 locus. Matched sections are from anterior to posterior. In control (A and B; Hif‐1αf/f; Wnt1Cre−) and cKO (C and D; Hif‐1αf/f; Wnt1Cre+) embryos, LacZ+ cells are present in the aorta, pulmonary artery and the semilunar valves. In the control embryo LacZ+ cells are evident in the rostral portion of the ventricular septum below the aortic valve (B). The outlet septum is absent in the cKO accounting for the outlet VSD. D, LacZ+ cells are observed in cKO in the abnormally positioned aortico‐pulmonic septum (arrow), which is incomplete resulting in PTA. Scale bars: 500 μm. Ao indicates aorta; cKO, conditional knock‐out; Hif, hypoxia‐inducible transcription factor; NCC, neural crest cells; pa, pulmonary artery; PTA, persistent truncus arteriosus; VSD, ventricular septal defect.
Mentions: Hif‐1αf/f mice were crossed with Rosa26‐LacZ mice to fate map NCCs migrating into the OFT using LacZ staining. In a Hif‐1αf/f; Wnt1Cre+ embryo with PTA, LacZ+ cells populate the great vessels and OFT, including the defective aortic‐pulmonic septum (Figures 6C and 6D; compare to control 6A and 6B). This suggests that HIF‐1α is not required within the NCCs for their migration into the cardiac OFT.

Bottom Line: The heart develops under reduced and varying oxygen concentrations, yet there is little understanding of oxygen metabolism in the normal and mal-development of the heart.ODD-Luc activity decreased in 2 stages, the first corresponding with the formation of a functional cardiovascular system for oxygen delivery at E15.5, and the second after birth consistent with complete oxygenation of the blood and tissues.Low oxygen concentrations and lack of oxygen reserve during a critical phase of heart organogenesis may provide a basis for vulnerability to the development of common septation and conotruncal heart defects.

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiovascular Medicine, University of Maryland School of Medicine, Baltimore, MD (D.K., S.A.F.).

Show MeSH
Related in: MedlinePlus