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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...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2016
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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. |
format | Online Article Text |
id | pubmed-4823603 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
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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