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Effects of blood oxygen saturation on pulmonary artery remodeling in an in vitro perfusion circuit model

BACKGROUND: Patients with transposition of the great arteries are likely to survive surgery despite severe pulmonary artery hypertension. However, the underlying mechanisms remain largely unknown. The present study aimed to test the hypothesis that high blood oxygen saturation may protect the pulmon...

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Autores principales: Liu, Yao, Wen, Bin, Zhang, Fengwen, Pan, Xiang-Bin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: AME Publishing Company 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107547/
https://www.ncbi.nlm.nih.gov/pubmed/34012567
http://dx.doi.org/10.21037/jtd-20-2124
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author Liu, Yao
Wen, Bin
Zhang, Fengwen
Pan, Xiang-Bin
author_facet Liu, Yao
Wen, Bin
Zhang, Fengwen
Pan, Xiang-Bin
author_sort Liu, Yao
collection PubMed
description BACKGROUND: Patients with transposition of the great arteries are likely to survive surgery despite severe pulmonary artery hypertension. However, the underlying mechanisms remain largely unknown. The present study aimed to test the hypothesis that high blood oxygen saturation may protect the pulmonary artery from remodeling. METHODS: An in vitro pulmonary artery perfusion model was successfully performed by connecting rabbit pulmonary artery to a closed perfusion circuit. Twenty-five rabbits were divided randomly into 5 groups according to exposure conditions: Normal Control (NC) group (unperfused normal pulmonary artery), High Saturation (HS) group (oxygen saturation range: 90–100%), Medium Saturation (MS) group (oxygen saturation: 65–75%); Low Saturation (LS) group (oxygen saturation: 40–50%), and anti-hypoxia inducible factor-1α (anti-HIF-1α) group (oxygen saturation range: 40–50%, and LW6, which is a novel HIF-1α inhibitor; was added). By staining and optical microscopy examination, pathological morphology was analyzed, and the protein expression levels of HIF-1α, angiotensin-II (Ang-II), endothelin-1 (ET-1), Rho-associated protein kinase-1 (Rock-1), and matrix metallopeptidase-2 (MMP-2) were determined by Western blotting. RESULTS: The amounts of elastin, muscle, and collagen and the protein levels of ET-1, HIF-1α, Rock-1, and MMP-2, increased significantly with decreased oxygen saturation in the perfusion circuit. A significant improvement in pathological morphology was observed in the anti-HIF1α group. The expression of HIF-1α, ET-1, Ang-II, Rock-1, and MMP-2 in the anti-HIF1α group was also significantly lower than that in the LS group. CONCLUSIONS: In the closed perfusion model, high blood oxygen saturation alleviated pulmonary vascular structural remodeling. Similar beneficial effects were observed when inhibiting the HIF-1α protein, suggesting a key role for HIF-1α in pulmonary artery remodeling.
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spelling pubmed-81075472021-05-18 Effects of blood oxygen saturation on pulmonary artery remodeling in an in vitro perfusion circuit model Liu, Yao Wen, Bin Zhang, Fengwen Pan, Xiang-Bin J Thorac Dis Original Article BACKGROUND: Patients with transposition of the great arteries are likely to survive surgery despite severe pulmonary artery hypertension. However, the underlying mechanisms remain largely unknown. The present study aimed to test the hypothesis that high blood oxygen saturation may protect the pulmonary artery from remodeling. METHODS: An in vitro pulmonary artery perfusion model was successfully performed by connecting rabbit pulmonary artery to a closed perfusion circuit. Twenty-five rabbits were divided randomly into 5 groups according to exposure conditions: Normal Control (NC) group (unperfused normal pulmonary artery), High Saturation (HS) group (oxygen saturation range: 90–100%), Medium Saturation (MS) group (oxygen saturation: 65–75%); Low Saturation (LS) group (oxygen saturation: 40–50%), and anti-hypoxia inducible factor-1α (anti-HIF-1α) group (oxygen saturation range: 40–50%, and LW6, which is a novel HIF-1α inhibitor; was added). By staining and optical microscopy examination, pathological morphology was analyzed, and the protein expression levels of HIF-1α, angiotensin-II (Ang-II), endothelin-1 (ET-1), Rho-associated protein kinase-1 (Rock-1), and matrix metallopeptidase-2 (MMP-2) were determined by Western blotting. RESULTS: The amounts of elastin, muscle, and collagen and the protein levels of ET-1, HIF-1α, Rock-1, and MMP-2, increased significantly with decreased oxygen saturation in the perfusion circuit. A significant improvement in pathological morphology was observed in the anti-HIF1α group. The expression of HIF-1α, ET-1, Ang-II, Rock-1, and MMP-2 in the anti-HIF1α group was also significantly lower than that in the LS group. CONCLUSIONS: In the closed perfusion model, high blood oxygen saturation alleviated pulmonary vascular structural remodeling. Similar beneficial effects were observed when inhibiting the HIF-1α protein, suggesting a key role for HIF-1α in pulmonary artery remodeling. AME Publishing Company 2021-04 /pmc/articles/PMC8107547/ /pubmed/34012567 http://dx.doi.org/10.21037/jtd-20-2124 Text en 2021 Journal of Thoracic Disease. All rights reserved. https://creativecommons.org/licenses/by-nc-nd/4.0/Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Original Article
Liu, Yao
Wen, Bin
Zhang, Fengwen
Pan, Xiang-Bin
Effects of blood oxygen saturation on pulmonary artery remodeling in an in vitro perfusion circuit model
title Effects of blood oxygen saturation on pulmonary artery remodeling in an in vitro perfusion circuit model
title_full Effects of blood oxygen saturation on pulmonary artery remodeling in an in vitro perfusion circuit model
title_fullStr Effects of blood oxygen saturation on pulmonary artery remodeling in an in vitro perfusion circuit model
title_full_unstemmed Effects of blood oxygen saturation on pulmonary artery remodeling in an in vitro perfusion circuit model
title_short Effects of blood oxygen saturation on pulmonary artery remodeling in an in vitro perfusion circuit model
title_sort effects of blood oxygen saturation on pulmonary artery remodeling in an in vitro perfusion circuit model
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107547/
https://www.ncbi.nlm.nih.gov/pubmed/34012567
http://dx.doi.org/10.21037/jtd-20-2124
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