Inhaled corticosteroids reduce senescence in endothelial progenitor cells from COPD patients
File(s)thoraxjnl-2020-216807.R2_Proof_hi.pdf (1.52 MB)
Accepted version
Author(s)
Type
Journal Article
Abstract
Cellular senescence contributes to the pathophysiology of chronic obstructive pulmonary
disease (COPD) and cardiovascular disease. Using endothelial-colony-forming-cells (ECFC),
we have demonstrated accelerated senescence in smokers and COPD patients compared to
non-smokers. Subgroup analysis suggests that ECFC from COPD patients on inhaledcorticosteroids (ICS) (n=14; 8 on ICS) exhibited significantly reduced senescence
(Senescence-associated-beta galactosidase activity, p21CIP1), markers of DNA damage
response (DDR) and IFN-γ-inducible-protein-10 compared to COPD patients not on ICS. In
vitro studies using human-umbilical-vein-endothelial-cells showed a protective effect of ICS
on the DDR, senescence and apoptosis caused by oxidative-stress, suggesting a protective
molecular mechanism of action of corticosteroids on endothelium.
disease (COPD) and cardiovascular disease. Using endothelial-colony-forming-cells (ECFC),
we have demonstrated accelerated senescence in smokers and COPD patients compared to
non-smokers. Subgroup analysis suggests that ECFC from COPD patients on inhaledcorticosteroids (ICS) (n=14; 8 on ICS) exhibited significantly reduced senescence
(Senescence-associated-beta galactosidase activity, p21CIP1), markers of DNA damage
response (DDR) and IFN-γ-inducible-protein-10 compared to COPD patients not on ICS. In
vitro studies using human-umbilical-vein-endothelial-cells showed a protective effect of ICS
on the DDR, senescence and apoptosis caused by oxidative-stress, suggesting a protective
molecular mechanism of action of corticosteroids on endothelium.
Date Acceptance
2021-11-19
Citation
Thorax, 77 (6)
ISSN
0040-6376
Publisher
BMJ Publishing Group
Journal / Book Title
Thorax
Volume
77
Issue
6
Copyright Statement
© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. http://creativecommons.org/licenses/by-nc/4.0/
This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
Sponsor
AstraZeneca AB
British Heart Foundation
Wellcome Trust
Rosetrees Trust
British Heart Foundation
Identifier
https://thorax.bmj.com/content/77/6/616.info
Grant Number
SEML-8N8DAB
PG/19/75/34686
093080/Z/10/Z
A2189/ M557F1
RE/18/4/34215
Subjects
Science & Technology
Life Sciences & Biomedicine
Respiratory System
COPD pharmacology
DNA-DAMAGE
SMOKERS
COPD pharmacology
Administration, Inhalation
Adrenal Cortex Hormones
Cellular Senescence
Endothelial Progenitor Cells
Humans
Pulmonary Disease, Chronic Obstructive
Humans
Pulmonary Disease, Chronic Obstructive
Adrenal Cortex Hormones
Administration, Inhalation
Endothelial Progenitor Cells
Cellular Senescence
Respiratory System
1103 Clinical Sciences
Publication Status
Published