Endothelial to mesenchymal transition is an active process in smokers and patients with early COPD contributing to pulmonary arterial pathology.

Autor:	Bhattarai P; Respiratory Translational Research Group, Department of Laboratory Medicine, School of Health Sciences, College of Health and Medicine, University of Tasmania, Launceston, TAS, Australia.; Launceston Respiratory and Sleep Centre, Launceston, TAS, Australia., Lu W; Respiratory Translational Research Group, Department of Laboratory Medicine, School of Health Sciences, College of Health and Medicine, University of Tasmania, Launceston, TAS, Australia.; Launceston Respiratory and Sleep Centre, Launceston, TAS, Australia., Hardikar A; Department of Cardiothoracic Surgery, Royal Hobart Hospital, Hobart, TAS, Australia.; Department of Cardiothoracic Surgery, The Royal Adelaide Hospital, Adelaide, SA, Australia., Dey S; Respiratory Translational Research Group, Department of Laboratory Medicine, School of Health Sciences, College of Health and Medicine, University of Tasmania, Launceston, TAS, Australia., Gaikwad AV; Respiratory Translational Research Group, Department of Laboratory Medicine, School of Health Sciences, College of Health and Medicine, University of Tasmania, Launceston, TAS, Australia., Shahzad AM; Respiratory Translational Research Group, Department of Laboratory Medicine, School of Health Sciences, College of Health and Medicine, University of Tasmania, Launceston, TAS, Australia., Chia C; Respiratory Translational Research Group, Department of Laboratory Medicine, School of Health Sciences, College of Health and Medicine, University of Tasmania, Launceston, TAS, Australia.; Launceston Respiratory and Sleep Centre, Launceston, TAS, Australia.; Department of Respiratory Medicine, Launceston General Hospital, Launceston, TAS, Australia., Williams A; Respiratory Translational Research Group, Department of Laboratory Medicine, School of Health Sciences, College of Health and Medicine, University of Tasmania, Launceston, TAS, Australia., Singhera GK; Department of Anaesthesiology, Pharmacology and Therapeutics, University of British Columbia, Vancouver, BC, Canada.; Centre for Heart Lung Innovation, St Paul's Hospital, Vancouver, BC, Canada., Hackett TL; Department of Anaesthesiology, Pharmacology and Therapeutics, University of British Columbia, Vancouver, BC, Canada.; Centre for Heart Lung Innovation, St Paul's Hospital, Vancouver, BC, Canada., Eapen MS; Respiratory Translational Research Group, Department of Laboratory Medicine, School of Health Sciences, College of Health and Medicine, University of Tasmania, Launceston, TAS, Australia., Sohal SS; Respiratory Translational Research Group, Department of Laboratory Medicine, School of Health Sciences, College of Health and Medicine, University of Tasmania, Launceston, TAS, Australia.; Launceston Respiratory and Sleep Centre, Launceston, TAS, Australia.
Jazyk:	angličtina
Zdroj:	ERJ open research [ERJ Open Res] 2024 Feb 12; Vol. 10 (1). Date of Electronic Publication: 2024 Feb 12 (Print Publication: 2024).
DOI:	10.1183/23120541.00767-2023
Abstrakt:	Background: We have previously reported pulmonary arterial remodelling in smokers and patients with early COPD, which can be attributed to endothelial to mesenchymal transition (EndMT). In this study, we aimed to evaluate if EndMT is an active mechanism in smokers and COPD. Methods: Immunohistochemical staining for the EndMT biomarkers CD31, N-cadherin, vimentin and S100A4 was done on lung resection tissue from 49 subjects. These comprised 15 nonsmoker controls (NC), six normal lung function smokers (NLFS), nine patients with small airway disease (SAD), nine current smokers with mild-moderate COPD (COPD-CS) and 10 ex-smokers with COPD (COPD-ES). Pulmonary arteries were analysed using Image ProPlus software v7.0. Results: We noted reduced junctional CD31 + endothelial cells (p<0.05) in the intimal layer of all smoking groups compared to NC. We also observed increased abundance of the mesenchymal markers N-cadherin (p<0.05) and vimentin (p<0.001) in all smoking groups and across all arterial sizes versus NC, except for N-cadherin in large arteries in COPD-CS. The abundance of S100A4 correlated with arterial thickness (small: r=0.29, p=0.05; medium: r=0.33, p=0.03; large: r=0.35, p=0.02). Vimentin in the small arterial wall negatively correlated with forced expiratory volume in 1 s/forced vital capacity (r= -0.35, p=0.02) and forced expiratory flow rate at 25-75% of forced vital capacity (r= -0.34, p=0.03), while increased cytoplasmic CD31 abundance in the intimal layer of medium and large arteries negatively correlated with predicted diffusing capacity of the lung for carbon monoxide (medium: r= -0.35, p=0.04; large: r= -0.39, p=0.03). Conclusion: This is the first study showing the acquisition of mesenchymal traits by pulmonary endothelial cells from NLFS, SAD and mild-moderate COPD patients through EndMT. This informs on the potential early origins of pulmonary hypertension in smokers and patients with early COPD. Competing Interests: Conflict of interest: S.S. Sohal reports honoraria for lectures from Chiesi; travel support from Chiesi, AstraZeneca and GSK; and research grants from Boehringer Ingelheim and Lung Therapeutics, outside the submitted work. S.S. Sohal has served on the small airway advisory board for Chiesi Australia, for which an honorarium has been received. Conflict of interest: All the other authors do not have any conflict of interest to declare. (Copyright ©The authors 2024.)
Databáze:	MEDLINE
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