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Aberrant cGMP signaling persists during recovery in mice with oxygen-induced pulmonary hypertension

Bronchopulmonary dysplasia (BPD), a common complication of preterm birth, is associated with pulmonary hypertension (PH) in 25% of infants with moderate to severe BPD. Neonatal mice exposed to hyperoxia for 14d develop lung disease similar to BPD, with evidence of associated PH. The cyclic guanosine...

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Autores principales: Perez, Marta, Lee, Keng Jin, Cardona, Herminio J., Taylor, Joann M., Robbins, Mary E., Waypa, Gregory B., Berkelhamer, Sara K., Farrow, Kathryn N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5549891/
https://www.ncbi.nlm.nih.gov/pubmed/28792962
http://dx.doi.org/10.1371/journal.pone.0180957
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author Perez, Marta
Lee, Keng Jin
Cardona, Herminio J.
Taylor, Joann M.
Robbins, Mary E.
Waypa, Gregory B.
Berkelhamer, Sara K.
Farrow, Kathryn N.
author_facet Perez, Marta
Lee, Keng Jin
Cardona, Herminio J.
Taylor, Joann M.
Robbins, Mary E.
Waypa, Gregory B.
Berkelhamer, Sara K.
Farrow, Kathryn N.
author_sort Perez, Marta
collection PubMed
description Bronchopulmonary dysplasia (BPD), a common complication of preterm birth, is associated with pulmonary hypertension (PH) in 25% of infants with moderate to severe BPD. Neonatal mice exposed to hyperoxia for 14d develop lung disease similar to BPD, with evidence of associated PH. The cyclic guanosine monophosphate (cGMP) signaling pathway has not been well studied in BPD-associated PH. In addition, there is little data about the natural history of hyperoxia-induced PH in mice or the utility of phosphodiesterase-5 (PDE5) inhibition in established disease. C57BL/6 mice were placed in room air or 75% O(2) within 24h of birth for 14d, followed by recovery in room air for an additional 7 days (21d). Additional pups were treated with either vehicle or sildenafil for 7d during room air recovery. Mean alveolar area, pulmonary artery (PA) medial wall thickness (MWT), RVH, and vessel density were evaluated at 21d. PA protein from 21d animals was analyzed for soluble guanylate cyclase (sGC) activity, PDE5 activity, and cGMP levels. Neonatal hyperoxia exposure results in persistent alveolar simplification, RVH, decreased vessel density, increased MWT, and disrupted cGMP signaling despite a period of room air recovery. Delayed treatment with sildenafil during room air recovery is associated with improved RVH and decreased PA PDE5 activity, but does not have significant effects on alveolar simplification, PA remodeling, or vessel density. These data are consistent with clinical studies suggesting inconsistent effects of sildenafil treatment in infants with BPD-associated PH.
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spelling pubmed-55498912017-08-15 Aberrant cGMP signaling persists during recovery in mice with oxygen-induced pulmonary hypertension Perez, Marta Lee, Keng Jin Cardona, Herminio J. Taylor, Joann M. Robbins, Mary E. Waypa, Gregory B. Berkelhamer, Sara K. Farrow, Kathryn N. PLoS One Research Article Bronchopulmonary dysplasia (BPD), a common complication of preterm birth, is associated with pulmonary hypertension (PH) in 25% of infants with moderate to severe BPD. Neonatal mice exposed to hyperoxia for 14d develop lung disease similar to BPD, with evidence of associated PH. The cyclic guanosine monophosphate (cGMP) signaling pathway has not been well studied in BPD-associated PH. In addition, there is little data about the natural history of hyperoxia-induced PH in mice or the utility of phosphodiesterase-5 (PDE5) inhibition in established disease. C57BL/6 mice were placed in room air or 75% O(2) within 24h of birth for 14d, followed by recovery in room air for an additional 7 days (21d). Additional pups were treated with either vehicle or sildenafil for 7d during room air recovery. Mean alveolar area, pulmonary artery (PA) medial wall thickness (MWT), RVH, and vessel density were evaluated at 21d. PA protein from 21d animals was analyzed for soluble guanylate cyclase (sGC) activity, PDE5 activity, and cGMP levels. Neonatal hyperoxia exposure results in persistent alveolar simplification, RVH, decreased vessel density, increased MWT, and disrupted cGMP signaling despite a period of room air recovery. Delayed treatment with sildenafil during room air recovery is associated with improved RVH and decreased PA PDE5 activity, but does not have significant effects on alveolar simplification, PA remodeling, or vessel density. These data are consistent with clinical studies suggesting inconsistent effects of sildenafil treatment in infants with BPD-associated PH. Public Library of Science 2017-08-09 /pmc/articles/PMC5549891/ /pubmed/28792962 http://dx.doi.org/10.1371/journal.pone.0180957 Text en © 2017 Perez 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 (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Perez, Marta
Lee, Keng Jin
Cardona, Herminio J.
Taylor, Joann M.
Robbins, Mary E.
Waypa, Gregory B.
Berkelhamer, Sara K.
Farrow, Kathryn N.
Aberrant cGMP signaling persists during recovery in mice with oxygen-induced pulmonary hypertension
title Aberrant cGMP signaling persists during recovery in mice with oxygen-induced pulmonary hypertension
title_full Aberrant cGMP signaling persists during recovery in mice with oxygen-induced pulmonary hypertension
title_fullStr Aberrant cGMP signaling persists during recovery in mice with oxygen-induced pulmonary hypertension
title_full_unstemmed Aberrant cGMP signaling persists during recovery in mice with oxygen-induced pulmonary hypertension
title_short Aberrant cGMP signaling persists during recovery in mice with oxygen-induced pulmonary hypertension
title_sort aberrant cgmp signaling persists during recovery in mice with oxygen-induced pulmonary hypertension
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5549891/
https://www.ncbi.nlm.nih.gov/pubmed/28792962
http://dx.doi.org/10.1371/journal.pone.0180957
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