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Systemic Maternal Inflammation and Neonatal Hyperoxia Induces Remodeling and Left Ventricular Dysfunction in Mice
AIMS: The impact of the neonatal environment on the development of adult cardiovascular disease is poorly understood. Systemic maternal inflammation is linked to growth retardation, preterm birth, and maturation deficits in the developing fetus. Often preterm or small-for-gestational age infants req...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3173376/ https://www.ncbi.nlm.nih.gov/pubmed/21935422 http://dx.doi.org/10.1371/journal.pone.0024544 |
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author | Velten, Markus Hutchinson, Kirk R. Gorr, Matthew W. Wold, Loren E. Lucchesi, Pamela A. Rogers, Lynette K. |
author_facet | Velten, Markus Hutchinson, Kirk R. Gorr, Matthew W. Wold, Loren E. Lucchesi, Pamela A. Rogers, Lynette K. |
author_sort | Velten, Markus |
collection | PubMed |
description | AIMS: The impact of the neonatal environment on the development of adult cardiovascular disease is poorly understood. Systemic maternal inflammation is linked to growth retardation, preterm birth, and maturation deficits in the developing fetus. Often preterm or small-for-gestational age infants require medical interventions such as oxygen therapy. The long-term pathological consequences of medical interventions on an immature physiology remain unknown. In the present study, we hypothesized that systemic maternal inflammation and neonatal hyperoxia exposure compromise cardiac structure, resulting in LV dysfunction during adulthood. METHODS AND RESULTS: Pregnant C3H/HeN mice were injected on embryonic day 16 (E16) with LPS (80 µg/kg; i.p.) or saline. Offspring were placed in room air (RA) or 85% O(2) for 14 days and subsequently maintained in RA. Cardiac echocardiography, cardiomyocyte contractility, and molecular analyses were performed. Echocardiography revealed persistent lower left ventricular fractional shortening with greater left ventricular end systolic diameter at 8 weeks in LPS/O(2) than in saline/RA mice. Isolated cardiomyocytes from LPS/O(2) mice had slower rates of contraction and relaxation, and a slower return to baseline length than cardiomyocytes isolated from saline/RA controls. α-/β-MHC ratio was increased and Connexin-43 levels decreased in LPS/O(2) mice at 8 weeks. Nox4 was reduced between day 3 and 14 and capillary density was lower at 8 weeks of life in LPS/O(2) mice. CONCLUSION: These results demonstrate that systemic maternal inflammation combined with neonatal hyperoxia exposure induces alterations in cardiac structure and function leading to cardiac failure in adulthood and supports the importance of the intrauterine and neonatal milieu on adult health. |
format | Online Article Text |
id | pubmed-3173376 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-31733762011-09-20 Systemic Maternal Inflammation and Neonatal Hyperoxia Induces Remodeling and Left Ventricular Dysfunction in Mice Velten, Markus Hutchinson, Kirk R. Gorr, Matthew W. Wold, Loren E. Lucchesi, Pamela A. Rogers, Lynette K. PLoS One Research Article AIMS: The impact of the neonatal environment on the development of adult cardiovascular disease is poorly understood. Systemic maternal inflammation is linked to growth retardation, preterm birth, and maturation deficits in the developing fetus. Often preterm or small-for-gestational age infants require medical interventions such as oxygen therapy. The long-term pathological consequences of medical interventions on an immature physiology remain unknown. In the present study, we hypothesized that systemic maternal inflammation and neonatal hyperoxia exposure compromise cardiac structure, resulting in LV dysfunction during adulthood. METHODS AND RESULTS: Pregnant C3H/HeN mice were injected on embryonic day 16 (E16) with LPS (80 µg/kg; i.p.) or saline. Offspring were placed in room air (RA) or 85% O(2) for 14 days and subsequently maintained in RA. Cardiac echocardiography, cardiomyocyte contractility, and molecular analyses were performed. Echocardiography revealed persistent lower left ventricular fractional shortening with greater left ventricular end systolic diameter at 8 weeks in LPS/O(2) than in saline/RA mice. Isolated cardiomyocytes from LPS/O(2) mice had slower rates of contraction and relaxation, and a slower return to baseline length than cardiomyocytes isolated from saline/RA controls. α-/β-MHC ratio was increased and Connexin-43 levels decreased in LPS/O(2) mice at 8 weeks. Nox4 was reduced between day 3 and 14 and capillary density was lower at 8 weeks of life in LPS/O(2) mice. CONCLUSION: These results demonstrate that systemic maternal inflammation combined with neonatal hyperoxia exposure induces alterations in cardiac structure and function leading to cardiac failure in adulthood and supports the importance of the intrauterine and neonatal milieu on adult health. Public Library of Science 2011-09-14 /pmc/articles/PMC3173376/ /pubmed/21935422 http://dx.doi.org/10.1371/journal.pone.0024544 Text en Velten et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Velten, Markus Hutchinson, Kirk R. Gorr, Matthew W. Wold, Loren E. Lucchesi, Pamela A. Rogers, Lynette K. Systemic Maternal Inflammation and Neonatal Hyperoxia Induces Remodeling and Left Ventricular Dysfunction in Mice |
title | Systemic Maternal Inflammation and Neonatal Hyperoxia Induces Remodeling and Left Ventricular Dysfunction in Mice |
title_full | Systemic Maternal Inflammation and Neonatal Hyperoxia Induces Remodeling and Left Ventricular Dysfunction in Mice |
title_fullStr | Systemic Maternal Inflammation and Neonatal Hyperoxia Induces Remodeling and Left Ventricular Dysfunction in Mice |
title_full_unstemmed | Systemic Maternal Inflammation and Neonatal Hyperoxia Induces Remodeling and Left Ventricular Dysfunction in Mice |
title_short | Systemic Maternal Inflammation and Neonatal Hyperoxia Induces Remodeling and Left Ventricular Dysfunction in Mice |
title_sort | systemic maternal inflammation and neonatal hyperoxia induces remodeling and left ventricular dysfunction in mice |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3173376/ https://www.ncbi.nlm.nih.gov/pubmed/21935422 http://dx.doi.org/10.1371/journal.pone.0024544 |
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