Inhaled corticosteroids reduce senescence in endothelial progenitor cells from patients with COPD.
Koralia E PaschalakiChristos RossiosCharis PericleousMairi MacLeodStephen RotheryGavin C DonaldsonJadwiga A WedzichaVassilis GorgoulisAnna M RandiPeter J BarnesPublished in: Thorax (2022)
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 patients with COPD compared with non-smokers. Subgroup analysis suggests that ECFC from patients with COPD on inhaled corticosteroids (ICS) (n=14; eight on ICS) exhibited significantly reduced senescence (Senescence-associated-beta galactosidase activity, p21 CIP1 ), markers of DNA damage response (DDR) and IFN-γ-inducible-protein-10 compared with patients with COPD 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.
Keyphrases
- endothelial cells
- chronic obstructive pulmonary disease
- dna damage
- lung function
- oxidative stress
- cardiovascular disease
- stress induced
- high glucose
- dna damage response
- cystic fibrosis
- induced apoptosis
- vascular endothelial growth factor
- cell cycle arrest
- smoking cessation
- dna repair
- endoplasmic reticulum stress
- type diabetes
- nitric oxide
- small molecule
- signaling pathway
- metabolic syndrome
- cell proliferation
- single molecule
- cardiovascular risk factors
- diabetic rats
- amino acid