Cardiorespiratory pathogenesis of sickle cell disease in a mouse model

Abstract The nature and development of cardiorespiratory impairments associated with sickle cell disease are poorly understood. Given that the mechanisms of these impairments cannot be addressed adequately in clinical studies, we characterized cardiorespiratory pathophysiology from birth to maturity...

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Autores principales:	Jun Ren, Xiuqing Ding, Marie Trudel, John J. Greer, Joanna E. MacLean
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/96ffcbb7a87d40e2b99bfef499c5008d
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spelling	oai:doaj.org-article:96ffcbb7a87d40e2b99bfef499c5008d2021-12-02T11:52:32ZCardiorespiratory pathogenesis of sickle cell disease in a mouse model10.1038/s41598-017-08860-82045-2322https://doaj.org/article/96ffcbb7a87d40e2b99bfef499c5008d2017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-08860-8https://doaj.org/toc/2045-2322Abstract The nature and development of cardiorespiratory impairments associated with sickle cell disease are poorly understood. Given that the mechanisms of these impairments cannot be addressed adequately in clinical studies, we characterized cardiorespiratory pathophysiology from birth to maturity in the sickle cell disease SAD mouse model. We identified two critical phases of respiratory dysfunction in SAD mice; the first prior to weaning and the second in adulthood. At postnatal day 3, 43% of SAD mice showed marked apneas, anemia, and pulmonary vascular congestion typical of acute chest syndrome; none of these mice survived to maturity. The remaining SAD mice had mild lung histological changes in room air with an altered respiratory pattern, seizures, and a high rate of death in response to hypoxia. Approximately half the SAD mice that survived to adulthood had an identifiable respiratory phenotype including baseline tachypnea at 7–8 months of age, restrictive lung disease, pulmonary hypertension, cardiac enlargement, lower total lung capacity, and pulmonary vascular congestion. All adult SAD mice demonstrated impairments in exercise capacity and response to hypoxia, with a more severe phenotype in the tachypneic mice. The model revealed distinguishable subgroups of SAD mice with cardiorespiratory pathophysiology mimicking the complications of human sickle cell disease.Jun RenXiuqing DingMarie TrudelJohn J. GreerJoanna E. MacLeanNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jun Ren Xiuqing Ding Marie Trudel John J. Greer Joanna E. MacLean Cardiorespiratory pathogenesis of sickle cell disease in a mouse model
description	Abstract The nature and development of cardiorespiratory impairments associated with sickle cell disease are poorly understood. Given that the mechanisms of these impairments cannot be addressed adequately in clinical studies, we characterized cardiorespiratory pathophysiology from birth to maturity in the sickle cell disease SAD mouse model. We identified two critical phases of respiratory dysfunction in SAD mice; the first prior to weaning and the second in adulthood. At postnatal day 3, 43% of SAD mice showed marked apneas, anemia, and pulmonary vascular congestion typical of acute chest syndrome; none of these mice survived to maturity. The remaining SAD mice had mild lung histological changes in room air with an altered respiratory pattern, seizures, and a high rate of death in response to hypoxia. Approximately half the SAD mice that survived to adulthood had an identifiable respiratory phenotype including baseline tachypnea at 7–8 months of age, restrictive lung disease, pulmonary hypertension, cardiac enlargement, lower total lung capacity, and pulmonary vascular congestion. All adult SAD mice demonstrated impairments in exercise capacity and response to hypoxia, with a more severe phenotype in the tachypneic mice. The model revealed distinguishable subgroups of SAD mice with cardiorespiratory pathophysiology mimicking the complications of human sickle cell disease.
format	article
author	Jun Ren Xiuqing Ding Marie Trudel John J. Greer Joanna E. MacLean
author_facet	Jun Ren Xiuqing Ding Marie Trudel John J. Greer Joanna E. MacLean
author_sort	Jun Ren
title	Cardiorespiratory pathogenesis of sickle cell disease in a mouse model
title_short	Cardiorespiratory pathogenesis of sickle cell disease in a mouse model
title_full	Cardiorespiratory pathogenesis of sickle cell disease in a mouse model
title_fullStr	Cardiorespiratory pathogenesis of sickle cell disease in a mouse model
title_full_unstemmed	Cardiorespiratory pathogenesis of sickle cell disease in a mouse model
title_sort	cardiorespiratory pathogenesis of sickle cell disease in a mouse model
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/96ffcbb7a87d40e2b99bfef499c5008d
work_keys_str_mv	AT junren cardiorespiratorypathogenesisofsicklecelldiseaseinamousemodel AT xiuqingding cardiorespiratorypathogenesisofsicklecelldiseaseinamousemodel AT marietrudel cardiorespiratorypathogenesisofsicklecelldiseaseinamousemodel AT johnjgreer cardiorespiratorypathogenesisofsicklecelldiseaseinamousemodel AT joannaemaclean cardiorespiratorypathogenesisofsicklecelldiseaseinamousemodel
_version_	1718394998052880384

Cardiorespiratory pathogenesis of sickle cell disease in a mouse model

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