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3D in vitro Model of Vascular Medial Thickening in Pulmonary Arterial Hypertension
In pulmonary arterial hypertension (PAH), excessive proliferation of pulmonary artery smooth muscle cells (PASMCs) causes vascular medial thickening. Medial thickening is a histopathological hallmark of pulmonary vascular remodeling, the central disease process driving PAH progression. Pulmonary vas...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7251161/ https://www.ncbi.nlm.nih.gov/pubmed/32509756 http://dx.doi.org/10.3389/fbioe.2020.00482 |
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author | Morii, Chiharu Tanaka, Hiroyoshi Y. Izushi, Yasuhisa Nakao, Natsumi Yamamoto, Masaya Matsubara, Hiromi Kano, Mitsunobu R. Ogawa, Aiko |
author_facet | Morii, Chiharu Tanaka, Hiroyoshi Y. Izushi, Yasuhisa Nakao, Natsumi Yamamoto, Masaya Matsubara, Hiromi Kano, Mitsunobu R. Ogawa, Aiko |
author_sort | Morii, Chiharu |
collection | PubMed |
description | In pulmonary arterial hypertension (PAH), excessive proliferation of pulmonary artery smooth muscle cells (PASMCs) causes vascular medial thickening. Medial thickening is a histopathological hallmark of pulmonary vascular remodeling, the central disease process driving PAH progression. Pulmonary vascular remodeling causes stenosis and/or obstruction of small pulmonary arteries. This leads to increased pulmonary vascular resistance, elevated pulmonary arterial pressure, and ultimately right heart failure. To improve the survival of PAH patients, which remains at approximately 60% at 3 years after diagnosis, the development of novel PAH-targeted drugs is desired. To this end, a detailed understanding of the mechanisms underlying excessive PASMC proliferation and the medial thickening that ensues is necessary. However, a lack of in vitro models that recapitulate medial thickening impedes our deeper understanding of the pathogenetic mechanisms involved. In the present study, we applied 3-dimensional (3D) cell culture technology to develop a novel in vitro model of the pulmonary artery medial layer using human PAH patient-derived PASMCs. The addition of platelet-derived growth factor (PDGF)-BB, a mitogen known to promote excessive PASMC proliferation in PAH, resulted in increased thickness of the 3D-PAH media tissues. Conversely, administration of the PDGF receptor inhibitor imatinib or other clinical PAH drugs inhibited this medial thickening-inducing effect of PDGF-BB. Altogether, by using 3D cell culture technology, we report the generation of an in vitro model of medial thickening in PAH, which had hitherto not been successfully modeled in vitro. This model is potentially useful for assessing the ability of candidate PAH drugs to suppress medial thickening. |
format | Online Article Text |
id | pubmed-7251161 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-72511612020-06-05 3D in vitro Model of Vascular Medial Thickening in Pulmonary Arterial Hypertension Morii, Chiharu Tanaka, Hiroyoshi Y. Izushi, Yasuhisa Nakao, Natsumi Yamamoto, Masaya Matsubara, Hiromi Kano, Mitsunobu R. Ogawa, Aiko Front Bioeng Biotechnol Bioengineering and Biotechnology In pulmonary arterial hypertension (PAH), excessive proliferation of pulmonary artery smooth muscle cells (PASMCs) causes vascular medial thickening. Medial thickening is a histopathological hallmark of pulmonary vascular remodeling, the central disease process driving PAH progression. Pulmonary vascular remodeling causes stenosis and/or obstruction of small pulmonary arteries. This leads to increased pulmonary vascular resistance, elevated pulmonary arterial pressure, and ultimately right heart failure. To improve the survival of PAH patients, which remains at approximately 60% at 3 years after diagnosis, the development of novel PAH-targeted drugs is desired. To this end, a detailed understanding of the mechanisms underlying excessive PASMC proliferation and the medial thickening that ensues is necessary. However, a lack of in vitro models that recapitulate medial thickening impedes our deeper understanding of the pathogenetic mechanisms involved. In the present study, we applied 3-dimensional (3D) cell culture technology to develop a novel in vitro model of the pulmonary artery medial layer using human PAH patient-derived PASMCs. The addition of platelet-derived growth factor (PDGF)-BB, a mitogen known to promote excessive PASMC proliferation in PAH, resulted in increased thickness of the 3D-PAH media tissues. Conversely, administration of the PDGF receptor inhibitor imatinib or other clinical PAH drugs inhibited this medial thickening-inducing effect of PDGF-BB. Altogether, by using 3D cell culture technology, we report the generation of an in vitro model of medial thickening in PAH, which had hitherto not been successfully modeled in vitro. This model is potentially useful for assessing the ability of candidate PAH drugs to suppress medial thickening. Frontiers Media S.A. 2020-05-20 /pmc/articles/PMC7251161/ /pubmed/32509756 http://dx.doi.org/10.3389/fbioe.2020.00482 Text en Copyright © 2020 Morii, Tanaka, Izushi, Nakao, Yamamoto, Matsubara, Kano and Ogawa. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Bioengineering and Biotechnology Morii, Chiharu Tanaka, Hiroyoshi Y. Izushi, Yasuhisa Nakao, Natsumi Yamamoto, Masaya Matsubara, Hiromi Kano, Mitsunobu R. Ogawa, Aiko 3D in vitro Model of Vascular Medial Thickening in Pulmonary Arterial Hypertension |
title | 3D in vitro Model of Vascular Medial Thickening in Pulmonary Arterial Hypertension |
title_full | 3D in vitro Model of Vascular Medial Thickening in Pulmonary Arterial Hypertension |
title_fullStr | 3D in vitro Model of Vascular Medial Thickening in Pulmonary Arterial Hypertension |
title_full_unstemmed | 3D in vitro Model of Vascular Medial Thickening in Pulmonary Arterial Hypertension |
title_short | 3D in vitro Model of Vascular Medial Thickening in Pulmonary Arterial Hypertension |
title_sort | 3d in vitro model of vascular medial thickening in pulmonary arterial hypertension |
topic | Bioengineering and Biotechnology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7251161/ https://www.ncbi.nlm.nih.gov/pubmed/32509756 http://dx.doi.org/10.3389/fbioe.2020.00482 |
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