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Endothelial cells from pulmonary endarterectomy specimens possess a high angiogenic potential and express high levels of hepatocyte growth factor

BACKGROUND: Impaired angiogenesis is assumed to be an important factor in the development of chronic thromboembolic pulmonary hypertension (CTEPH). However, the role of endothelial cells (ECs) in CTEPH remains unclear. The aim of this study was to investigate the angiogenic potential of ECs from pul...

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Autores principales: Naito, Akira, Sakao, Seiichiro, Lang, Irene M., Voelkel, Norbert F., Jujo, Takayuki, Ishida, Keiichi, Sugiura, Toshihiko, Matsumiya, Goro, Yoshino, Ichiro, Tanabe, Nobuhiro, Tatsumi, Koichiro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6310963/
https://www.ncbi.nlm.nih.gov/pubmed/30594174
http://dx.doi.org/10.1186/s12890-018-0769-3
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author Naito, Akira
Sakao, Seiichiro
Lang, Irene M.
Voelkel, Norbert F.
Jujo, Takayuki
Ishida, Keiichi
Sugiura, Toshihiko
Matsumiya, Goro
Yoshino, Ichiro
Tanabe, Nobuhiro
Tatsumi, Koichiro
author_facet Naito, Akira
Sakao, Seiichiro
Lang, Irene M.
Voelkel, Norbert F.
Jujo, Takayuki
Ishida, Keiichi
Sugiura, Toshihiko
Matsumiya, Goro
Yoshino, Ichiro
Tanabe, Nobuhiro
Tatsumi, Koichiro
author_sort Naito, Akira
collection PubMed
description BACKGROUND: Impaired angiogenesis is assumed to be an important factor in the development of chronic thromboembolic pulmonary hypertension (CTEPH). However, the role of endothelial cells (ECs) in CTEPH remains unclear. The aim of this study was to investigate the angiogenic potential of ECs from pulmonary endarterectomy (PEA) specimens. METHODS: We isolated ECs from PEA specimens (CTEPH-ECs) and control EC lines from the intact pulmonary arteries of patients with peripheral lung cancers, using a MACS system. These cells were analyzed in vitro including PCR-array analysis, and the PEA specimens were analyzed with immunohistochemistry. Additionally, the serum HGF levels were determined in CTEPH patients. RESULTS: A three-dimensional culture assay revealed that CTEPH-ECs were highly angiogenic. An angiogenesis-focused gene PCR array revealed a high expression of hepatocyte growth factor (HGF) in CTEPH-ECs. The high expression of HGF was also confirmed in the supernatant extracted from PEA specimens. The immunohistochemical analysis showed expression of HGF on the surface of the thrombus vessels. The serum HGF levels in CTEPH patients were higher than those in pulmonary thromboembolism survivors. CONCLUSION: Our study suggests that there are ECs with pro-angiogenetic character and high expression of HGF in PEA specimens. It remains unknown how these results are attributable to the etiology. However, further investigation focused on the HGF pathway may provide novel diagnostic and therapeutic tools for patients with CTEPH. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12890-018-0769-3) contains supplementary material, which is available to authorized users.
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spelling pubmed-63109632019-01-07 Endothelial cells from pulmonary endarterectomy specimens possess a high angiogenic potential and express high levels of hepatocyte growth factor Naito, Akira Sakao, Seiichiro Lang, Irene M. Voelkel, Norbert F. Jujo, Takayuki Ishida, Keiichi Sugiura, Toshihiko Matsumiya, Goro Yoshino, Ichiro Tanabe, Nobuhiro Tatsumi, Koichiro BMC Pulm Med Research Article BACKGROUND: Impaired angiogenesis is assumed to be an important factor in the development of chronic thromboembolic pulmonary hypertension (CTEPH). However, the role of endothelial cells (ECs) in CTEPH remains unclear. The aim of this study was to investigate the angiogenic potential of ECs from pulmonary endarterectomy (PEA) specimens. METHODS: We isolated ECs from PEA specimens (CTEPH-ECs) and control EC lines from the intact pulmonary arteries of patients with peripheral lung cancers, using a MACS system. These cells were analyzed in vitro including PCR-array analysis, and the PEA specimens were analyzed with immunohistochemistry. Additionally, the serum HGF levels were determined in CTEPH patients. RESULTS: A three-dimensional culture assay revealed that CTEPH-ECs were highly angiogenic. An angiogenesis-focused gene PCR array revealed a high expression of hepatocyte growth factor (HGF) in CTEPH-ECs. The high expression of HGF was also confirmed in the supernatant extracted from PEA specimens. The immunohistochemical analysis showed expression of HGF on the surface of the thrombus vessels. The serum HGF levels in CTEPH patients were higher than those in pulmonary thromboembolism survivors. CONCLUSION: Our study suggests that there are ECs with pro-angiogenetic character and high expression of HGF in PEA specimens. It remains unknown how these results are attributable to the etiology. However, further investigation focused on the HGF pathway may provide novel diagnostic and therapeutic tools for patients with CTEPH. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12890-018-0769-3) contains supplementary material, which is available to authorized users. BioMed Central 2018-12-29 /pmc/articles/PMC6310963/ /pubmed/30594174 http://dx.doi.org/10.1186/s12890-018-0769-3 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Naito, Akira
Sakao, Seiichiro
Lang, Irene M.
Voelkel, Norbert F.
Jujo, Takayuki
Ishida, Keiichi
Sugiura, Toshihiko
Matsumiya, Goro
Yoshino, Ichiro
Tanabe, Nobuhiro
Tatsumi, Koichiro
Endothelial cells from pulmonary endarterectomy specimens possess a high angiogenic potential and express high levels of hepatocyte growth factor
title Endothelial cells from pulmonary endarterectomy specimens possess a high angiogenic potential and express high levels of hepatocyte growth factor
title_full Endothelial cells from pulmonary endarterectomy specimens possess a high angiogenic potential and express high levels of hepatocyte growth factor
title_fullStr Endothelial cells from pulmonary endarterectomy specimens possess a high angiogenic potential and express high levels of hepatocyte growth factor
title_full_unstemmed Endothelial cells from pulmonary endarterectomy specimens possess a high angiogenic potential and express high levels of hepatocyte growth factor
title_short Endothelial cells from pulmonary endarterectomy specimens possess a high angiogenic potential and express high levels of hepatocyte growth factor
title_sort endothelial cells from pulmonary endarterectomy specimens possess a high angiogenic potential and express high levels of hepatocyte growth factor
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6310963/
https://www.ncbi.nlm.nih.gov/pubmed/30594174
http://dx.doi.org/10.1186/s12890-018-0769-3
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