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Ebselen abolishes vascular dysfunction in influenza A virus-induced exacerbations of cigarette smoke-induced lung inflammation in mice
People with chronic obstructive pulmonary disease (COPD) are susceptible to respiratory infections which exacerbate pulmonary and/or cardiovascular complications, increasing their likelihood of death. The mechanisms driving these complications remain unknown but increased oxidative stress has been i...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Portland Press Ltd.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9069468/ https://www.ncbi.nlm.nih.gov/pubmed/35343564 http://dx.doi.org/10.1042/CS20211090 |
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author | Brassington, Kurt Chan, Stanley M.H. De Luca, Simone N. Dobric, Aleksandar Almerdasi, Suleman A. Mou, Kevin Seow, Huei Jiunn Oseghale, Osezua Bozinovski, Steven Selemidis, Stavros Vlahos, Ross |
author_facet | Brassington, Kurt Chan, Stanley M.H. De Luca, Simone N. Dobric, Aleksandar Almerdasi, Suleman A. Mou, Kevin Seow, Huei Jiunn Oseghale, Osezua Bozinovski, Steven Selemidis, Stavros Vlahos, Ross |
author_sort | Brassington, Kurt |
collection | PubMed |
description | People with chronic obstructive pulmonary disease (COPD) are susceptible to respiratory infections which exacerbate pulmonary and/or cardiovascular complications, increasing their likelihood of death. The mechanisms driving these complications remain unknown but increased oxidative stress has been implicated. Here we investigated whether influenza A virus (IAV) infection, following chronic cigarette smoke (CS) exposure, worsens vascular function and if so, whether the antioxidant ebselen alleviates this vascular dysfunction. Male BALB/c mice were exposed to either room air or CS for 8 weeks followed by inoculation with IAV (Mem71, 1 × 10(4.5) pfu). Mice were treated with ebselen (10 mg/kg) or vehicle (5% w/v CM-cellulose in water) daily. Mice were culled 3- and 10-days post-infection, and their lungs lavaged to assess inflammation. The thoracic aorta was excised to investigate endothelial and smooth muscle dilator responses, expression of key vasodilatory and oxidative stress modulators, infiltrating immune cells and vascular remodelling. CS increased lung inflammation and caused significant vascular endothelial dysfunction, which was worsened by IAV infection. CS-driven increases in vascular oxidative stress, aortic wall remodelling and suppression of endothelial nitric oxide synthase (eNOS) were not affected by IAV infection. CS and IAV infection significantly enhanced T cell recruitment into the aortic wall. Ebselen abolished the exaggerated lung inflammation, vascular dysfunction and increased T cell infiltration in CS and IAV-infected mice. Our findings showed that ebselen treatment abolished vascular dysfunction in IAV-induced exacerbations of CS-induced lung inflammation indicating it may have potential for the treatment of cardiovascular comorbidities seen in acute exacerbations of COPD (AECOPD). |
format | Online Article Text |
id | pubmed-9069468 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Portland Press Ltd. |
record_format | MEDLINE/PubMed |
spelling | pubmed-90694682022-05-12 Ebselen abolishes vascular dysfunction in influenza A virus-induced exacerbations of cigarette smoke-induced lung inflammation in mice Brassington, Kurt Chan, Stanley M.H. De Luca, Simone N. Dobric, Aleksandar Almerdasi, Suleman A. Mou, Kevin Seow, Huei Jiunn Oseghale, Osezua Bozinovski, Steven Selemidis, Stavros Vlahos, Ross Clin Sci (Lond) Respiratory System People with chronic obstructive pulmonary disease (COPD) are susceptible to respiratory infections which exacerbate pulmonary and/or cardiovascular complications, increasing their likelihood of death. The mechanisms driving these complications remain unknown but increased oxidative stress has been implicated. Here we investigated whether influenza A virus (IAV) infection, following chronic cigarette smoke (CS) exposure, worsens vascular function and if so, whether the antioxidant ebselen alleviates this vascular dysfunction. Male BALB/c mice were exposed to either room air or CS for 8 weeks followed by inoculation with IAV (Mem71, 1 × 10(4.5) pfu). Mice were treated with ebselen (10 mg/kg) or vehicle (5% w/v CM-cellulose in water) daily. Mice were culled 3- and 10-days post-infection, and their lungs lavaged to assess inflammation. The thoracic aorta was excised to investigate endothelial and smooth muscle dilator responses, expression of key vasodilatory and oxidative stress modulators, infiltrating immune cells and vascular remodelling. CS increased lung inflammation and caused significant vascular endothelial dysfunction, which was worsened by IAV infection. CS-driven increases in vascular oxidative stress, aortic wall remodelling and suppression of endothelial nitric oxide synthase (eNOS) were not affected by IAV infection. CS and IAV infection significantly enhanced T cell recruitment into the aortic wall. Ebselen abolished the exaggerated lung inflammation, vascular dysfunction and increased T cell infiltration in CS and IAV-infected mice. Our findings showed that ebselen treatment abolished vascular dysfunction in IAV-induced exacerbations of CS-induced lung inflammation indicating it may have potential for the treatment of cardiovascular comorbidities seen in acute exacerbations of COPD (AECOPD). Portland Press Ltd. 2022-04 2022-04-21 /pmc/articles/PMC9069468/ /pubmed/35343564 http://dx.doi.org/10.1042/CS20211090 Text en © 2022 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/) . |
spellingShingle | Respiratory System Brassington, Kurt Chan, Stanley M.H. De Luca, Simone N. Dobric, Aleksandar Almerdasi, Suleman A. Mou, Kevin Seow, Huei Jiunn Oseghale, Osezua Bozinovski, Steven Selemidis, Stavros Vlahos, Ross Ebselen abolishes vascular dysfunction in influenza A virus-induced exacerbations of cigarette smoke-induced lung inflammation in mice |
title | Ebselen abolishes vascular dysfunction in influenza A virus-induced exacerbations of cigarette smoke-induced lung inflammation in mice |
title_full | Ebselen abolishes vascular dysfunction in influenza A virus-induced exacerbations of cigarette smoke-induced lung inflammation in mice |
title_fullStr | Ebselen abolishes vascular dysfunction in influenza A virus-induced exacerbations of cigarette smoke-induced lung inflammation in mice |
title_full_unstemmed | Ebselen abolishes vascular dysfunction in influenza A virus-induced exacerbations of cigarette smoke-induced lung inflammation in mice |
title_short | Ebselen abolishes vascular dysfunction in influenza A virus-induced exacerbations of cigarette smoke-induced lung inflammation in mice |
title_sort | ebselen abolishes vascular dysfunction in influenza a virus-induced exacerbations of cigarette smoke-induced lung inflammation in mice |
topic | Respiratory System |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9069468/ https://www.ncbi.nlm.nih.gov/pubmed/35343564 http://dx.doi.org/10.1042/CS20211090 |
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