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Ion channels as convergence points in the pathology of pulmonary arterial hypertension
Pulmonary arterial hypertension (PAH) is a fatal disease of the cardiopulmonary system that lacks curative treatments. The main pathological event in PAH is elevated vascular resistance in the pulmonary circulation, caused by abnormal vasoconstriction and vascular remodelling. Ion channels are key d...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Portland Press Ltd.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8421048/ https://www.ncbi.nlm.nih.gov/pubmed/34346486 http://dx.doi.org/10.1042/BST20210538 |
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author | Jouen-Tachoire, Thibault R. H. Tucker, Stephen J. Tammaro, Paolo |
author_facet | Jouen-Tachoire, Thibault R. H. Tucker, Stephen J. Tammaro, Paolo |
author_sort | Jouen-Tachoire, Thibault R. H. |
collection | PubMed |
description | Pulmonary arterial hypertension (PAH) is a fatal disease of the cardiopulmonary system that lacks curative treatments. The main pathological event in PAH is elevated vascular resistance in the pulmonary circulation, caused by abnormal vasoconstriction and vascular remodelling. Ion channels are key determinants of vascular smooth muscle tone and homeostasis, and four PAH channelopathies (KCNK3, ABCC8, KCNA5, TRPC6) have been identified so far. However, the contribution of ion channels in other forms of PAH, which account for the majority of PAH patients, has been less well characterised. Here we reason that a variety of triggers of PAH (e.g. BMPR2 mutations, hypoxia, anorectic drugs) that impact channel function may contribute to the onset of the disease. We review the molecular mechanisms by which these ‘extrinsic’ factors converge on ion channels and provoke their dysregulation to promote the development of PAH. Ion channels of the pulmonary vasculature are therefore promising therapeutic targets because of the modulation they provide to both vasomotor tone and proliferation of arterial smooth muscle cells. |
format | Online Article Text |
id | pubmed-8421048 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Portland Press Ltd. |
record_format | MEDLINE/PubMed |
spelling | pubmed-84210482021-09-14 Ion channels as convergence points in the pathology of pulmonary arterial hypertension Jouen-Tachoire, Thibault R. H. Tucker, Stephen J. Tammaro, Paolo Biochem Soc Trans Review Articles Pulmonary arterial hypertension (PAH) is a fatal disease of the cardiopulmonary system that lacks curative treatments. The main pathological event in PAH is elevated vascular resistance in the pulmonary circulation, caused by abnormal vasoconstriction and vascular remodelling. Ion channels are key determinants of vascular smooth muscle tone and homeostasis, and four PAH channelopathies (KCNK3, ABCC8, KCNA5, TRPC6) have been identified so far. However, the contribution of ion channels in other forms of PAH, which account for the majority of PAH patients, has been less well characterised. Here we reason that a variety of triggers of PAH (e.g. BMPR2 mutations, hypoxia, anorectic drugs) that impact channel function may contribute to the onset of the disease. We review the molecular mechanisms by which these ‘extrinsic’ factors converge on ion channels and provoke their dysregulation to promote the development of PAH. Ion channels of the pulmonary vasculature are therefore promising therapeutic targets because of the modulation they provide to both vasomotor tone and proliferation of arterial smooth muscle cells. Portland Press Ltd. 2021-08-27 2021-08-04 /pmc/articles/PMC8421048/ /pubmed/34346486 http://dx.doi.org/10.1042/BST20210538 Text en © 2021 The Author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY) (https://creativecommons.org/licenses/by/4.0/) . Open access for this article was enabled by the participation of University of Oxford in an all-inclusive Read & Publish pilot with Portland Press and the Biochemical Society under a transformative agreement with JISC. |
spellingShingle | Review Articles Jouen-Tachoire, Thibault R. H. Tucker, Stephen J. Tammaro, Paolo Ion channels as convergence points in the pathology of pulmonary arterial hypertension |
title | Ion channels as convergence points in the pathology of pulmonary arterial hypertension |
title_full | Ion channels as convergence points in the pathology of pulmonary arterial hypertension |
title_fullStr | Ion channels as convergence points in the pathology of pulmonary arterial hypertension |
title_full_unstemmed | Ion channels as convergence points in the pathology of pulmonary arterial hypertension |
title_short | Ion channels as convergence points in the pathology of pulmonary arterial hypertension |
title_sort | ion channels as convergence points in the pathology of pulmonary arterial hypertension |
topic | Review Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8421048/ https://www.ncbi.nlm.nih.gov/pubmed/34346486 http://dx.doi.org/10.1042/BST20210538 |
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