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The Na(+)/H(+) exchanger contributes to increased smooth muscle proliferation and migration in a rat model of pulmonary arterial hypertension

Increased muscularity of small pulmonary vessels, involving enhanced proliferation and migration of pulmonary arterial smooth muscle cells (PASMCs), is a key component of the vascular remodeling underlying the development of pulmonary hypertension (PH). Stimuli such as growth factors and hypoxia ind...

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Autores principales: Huetsch, John C., Jiang, Haiyang, Larrain, Carolina, Shimoda, Larissa A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4823603/
https://www.ncbi.nlm.nih.gov/pubmed/26997630
http://dx.doi.org/10.14814/phy2.12729
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author Huetsch, John C.
Jiang, Haiyang
Larrain, Carolina
Shimoda, Larissa A.
author_facet Huetsch, John C.
Jiang, Haiyang
Larrain, Carolina
Shimoda, Larissa A.
author_sort Huetsch, John C.
collection PubMed
description Increased muscularity of small pulmonary vessels, involving enhanced proliferation and migration of pulmonary arterial smooth muscle cells (PASMCs), is a key component of the vascular remodeling underlying the development of pulmonary hypertension (PH). Stimuli such as growth factors and hypoxia induce PASMC alkalinization, proliferation, and migration through upregulation of the Na(+)/H(+) exchanger (NHE), inhibition of which prevents the development of hypoxia‐induced vascular remodeling and PH. We wanted to explore whether NHE was also necessary for pathologic PASMC proliferation and migration in a model of pulmonary arterial hypertension (PAH), a severe form of PH not associated with persistent hypoxia. PASMCs were isolated from rats exposed to SU5416‐hypoxia (SuHx) followed by return to normoxia and from vehicle controls. We measured resting intracellular pH (pH (i)) and NHE activity using the pH‐sensitive fluorescent dye BCECF‐AM. PASMC proliferation and migration were assessed using BrdU incorporation and transwell filters, respectively. NHE activity was increased in SuHx PASMCs, although resting pH (i) was unchanged. SuHx PASMCs also exhibited increased proliferation and migration relative to controls, which was attenuated in the setting of pharmacologic inhibition of NHE. Our findings suggest that increased NHE activity contributes to pathologic PASMC function in the SuHx model of PAH, although this effect does not appear to be mediated by global changes in pH (i) homeostasis.
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spelling pubmed-48236032016-04-18 The Na(+)/H(+) exchanger contributes to increased smooth muscle proliferation and migration in a rat model of pulmonary arterial hypertension Huetsch, John C. Jiang, Haiyang Larrain, Carolina Shimoda, Larissa A. Physiol Rep Original Research Increased muscularity of small pulmonary vessels, involving enhanced proliferation and migration of pulmonary arterial smooth muscle cells (PASMCs), is a key component of the vascular remodeling underlying the development of pulmonary hypertension (PH). Stimuli such as growth factors and hypoxia induce PASMC alkalinization, proliferation, and migration through upregulation of the Na(+)/H(+) exchanger (NHE), inhibition of which prevents the development of hypoxia‐induced vascular remodeling and PH. We wanted to explore whether NHE was also necessary for pathologic PASMC proliferation and migration in a model of pulmonary arterial hypertension (PAH), a severe form of PH not associated with persistent hypoxia. PASMCs were isolated from rats exposed to SU5416‐hypoxia (SuHx) followed by return to normoxia and from vehicle controls. We measured resting intracellular pH (pH (i)) and NHE activity using the pH‐sensitive fluorescent dye BCECF‐AM. PASMC proliferation and migration were assessed using BrdU incorporation and transwell filters, respectively. NHE activity was increased in SuHx PASMCs, although resting pH (i) was unchanged. SuHx PASMCs also exhibited increased proliferation and migration relative to controls, which was attenuated in the setting of pharmacologic inhibition of NHE. Our findings suggest that increased NHE activity contributes to pathologic PASMC function in the SuHx model of PAH, although this effect does not appear to be mediated by global changes in pH (i) homeostasis. John Wiley and Sons Inc. 2016-03-20 /pmc/articles/PMC4823603/ /pubmed/26997630 http://dx.doi.org/10.14814/phy2.12729 Text en © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Research
Huetsch, John C.
Jiang, Haiyang
Larrain, Carolina
Shimoda, Larissa A.
The Na(+)/H(+) exchanger contributes to increased smooth muscle proliferation and migration in a rat model of pulmonary arterial hypertension
title The Na(+)/H(+) exchanger contributes to increased smooth muscle proliferation and migration in a rat model of pulmonary arterial hypertension
title_full The Na(+)/H(+) exchanger contributes to increased smooth muscle proliferation and migration in a rat model of pulmonary arterial hypertension
title_fullStr The Na(+)/H(+) exchanger contributes to increased smooth muscle proliferation and migration in a rat model of pulmonary arterial hypertension
title_full_unstemmed The Na(+)/H(+) exchanger contributes to increased smooth muscle proliferation and migration in a rat model of pulmonary arterial hypertension
title_short The Na(+)/H(+) exchanger contributes to increased smooth muscle proliferation and migration in a rat model of pulmonary arterial hypertension
title_sort na(+)/h(+) exchanger contributes to increased smooth muscle proliferation and migration in a rat model of pulmonary arterial hypertension
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4823603/
https://www.ncbi.nlm.nih.gov/pubmed/26997630
http://dx.doi.org/10.14814/phy2.12729
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