Identification of exercise‐regulated genes in mice exposed to cigarette smoke

Abstract Cigarette smoke (CS) is the major risk factor for COPD and is linked to cardiopulmonary dysfunction. Exercise training as part of pulmonary rehabilitation is recommended for all COPD patients. It has several physiological benefits, but the mechanisms involved remain poorly defined. Here, we...

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Main Authors: Lars Aakerøy, Chew W. Cheng, Pavla Sustova, Nathan R. Scrimgeour, Sissel Gyrid Freim Wahl, Sigurd Steinshamn, T. Scott Bowen, Eivind Brønstad
Format: Article
Language:English
Published: Wiley 2022-11-01
Series:Physiological Reports
Subjects:
Online Access:https://doi.org/10.14814/phy2.15505
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author Lars Aakerøy
Chew W. Cheng
Pavla Sustova
Nathan R. Scrimgeour
Sissel Gyrid Freim Wahl
Sigurd Steinshamn
T. Scott Bowen
Eivind Brønstad
author_facet Lars Aakerøy
Chew W. Cheng
Pavla Sustova
Nathan R. Scrimgeour
Sissel Gyrid Freim Wahl
Sigurd Steinshamn
T. Scott Bowen
Eivind Brønstad
author_sort Lars Aakerøy
collection DOAJ
description Abstract Cigarette smoke (CS) is the major risk factor for COPD and is linked to cardiopulmonary dysfunction. Exercise training as part of pulmonary rehabilitation is recommended for all COPD patients. It has several physiological benefits, but the mechanisms involved remain poorly defined. Here, we employed transcriptomic profiling and examined lung endothelium to investigate novel interactions between exercise and CS on cardiopulmonary alterations. Mice were exposed to 20 weeks of CS, CS + 6 weeks of high‐intensity interval training on a treadmill, or control. Lung and cardiac (left and right ventricle) tissue were harvested and RNA‐sequencing was performed and validated with RT‐qPCR. Immunohistochemistry assessed pulmonary arteriolar changes. Transcriptome analysis between groups revealed 37 significantly regulated genes in the lung, 21 genes in the left ventricle, and 43 genes in the right ventricle (likelihood‐ratio test). Validated genes that showed interaction between exercise and CS included angiotensinogen (p = 0.002) and resistin‐like alpha (p = 0.019) in left ventricle, with prostacyclin synthetase different in pulmonary arterioles (p = 0.004). Transcriptomic profiling revealed changes in pulmonary and cardiac tissue following exposure to CS, with exercise training exerting rescue effects. Exercise‐regulated genes included angiotensinogen and resistin‐like alpha, however, it remains unclear if these represent potential candidate genes or biomarkers that could play a role during pulmonary rehabilitation.
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spelling doaj.art-4b1e10af221a443aaa18c8aef8f5310f2022-12-22T03:41:33ZengWileyPhysiological Reports2051-817X2022-11-011021n/an/a10.14814/phy2.15505Identification of exercise‐regulated genes in mice exposed to cigarette smokeLars Aakerøy0Chew W. Cheng1Pavla Sustova2Nathan R. Scrimgeour3Sissel Gyrid Freim Wahl4Sigurd Steinshamn5T. Scott Bowen6Eivind Brønstad7Department of Thoracic Medicine St. Olavs Hospital, Trondheim University Hospital Trondheim NorwayLeeds Institute of Cardiovascular and Metabolic Medicine University of Leeds Leeds UKDepartment of Pathology St. Olav Hospital, Trondheim University Hospital Trondheim NorwayDepartment of Circulation and Medical Imaging, Faculty of Medicine and Health Science Norwegian University of Science and Technology Trondheim NorwayDepartment of Pathology St. Olav Hospital, Trondheim University Hospital Trondheim NorwayDepartment of Thoracic Medicine St. Olavs Hospital, Trondheim University Hospital Trondheim NorwaySchool of Biomedical Sciences, Faculty of Biological Sciences University of Leeds Leeds UKDepartment of Thoracic Medicine St. Olavs Hospital, Trondheim University Hospital Trondheim NorwayAbstract Cigarette smoke (CS) is the major risk factor for COPD and is linked to cardiopulmonary dysfunction. Exercise training as part of pulmonary rehabilitation is recommended for all COPD patients. It has several physiological benefits, but the mechanisms involved remain poorly defined. Here, we employed transcriptomic profiling and examined lung endothelium to investigate novel interactions between exercise and CS on cardiopulmonary alterations. Mice were exposed to 20 weeks of CS, CS + 6 weeks of high‐intensity interval training on a treadmill, or control. Lung and cardiac (left and right ventricle) tissue were harvested and RNA‐sequencing was performed and validated with RT‐qPCR. Immunohistochemistry assessed pulmonary arteriolar changes. Transcriptome analysis between groups revealed 37 significantly regulated genes in the lung, 21 genes in the left ventricle, and 43 genes in the right ventricle (likelihood‐ratio test). Validated genes that showed interaction between exercise and CS included angiotensinogen (p = 0.002) and resistin‐like alpha (p = 0.019) in left ventricle, with prostacyclin synthetase different in pulmonary arterioles (p = 0.004). Transcriptomic profiling revealed changes in pulmonary and cardiac tissue following exposure to CS, with exercise training exerting rescue effects. Exercise‐regulated genes included angiotensinogen and resistin‐like alpha, however, it remains unclear if these represent potential candidate genes or biomarkers that could play a role during pulmonary rehabilitation.https://doi.org/10.14814/phy2.15505Cigarette smokeendothelialhigh‐intensity interval trainingtranscriptome
spellingShingle Lars Aakerøy
Chew W. Cheng
Pavla Sustova
Nathan R. Scrimgeour
Sissel Gyrid Freim Wahl
Sigurd Steinshamn
T. Scott Bowen
Eivind Brønstad
Identification of exercise‐regulated genes in mice exposed to cigarette smoke
Physiological Reports
Cigarette smoke
endothelial
high‐intensity interval training
transcriptome
title Identification of exercise‐regulated genes in mice exposed to cigarette smoke
title_full Identification of exercise‐regulated genes in mice exposed to cigarette smoke
title_fullStr Identification of exercise‐regulated genes in mice exposed to cigarette smoke
title_full_unstemmed Identification of exercise‐regulated genes in mice exposed to cigarette smoke
title_short Identification of exercise‐regulated genes in mice exposed to cigarette smoke
title_sort identification of exercise regulated genes in mice exposed to cigarette smoke
topic Cigarette smoke
endothelial
high‐intensity interval training
transcriptome
url https://doi.org/10.14814/phy2.15505
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