Author:
Naz Shama,Kolmert Johan,Yang Mingxing,Reinke Stacey N.,Kamleh Muhammad Anas,Snowden Stuart,Heyder Tina,Levänen Bettina,Erle David J.,Sköld C. Magnus,Wheelock Åsa M.,Wheelock Craig E.
Abstract
Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease and a leading cause of mortality and morbidity worldwide. The aim of this study was to investigate the sex dependency of circulating metabolic profiles in COPD.Serum from healthy never-smokers (healthy), smokers with normal lung function (smokers), and smokers with COPD (COPD; Global Initiative for Chronic Obstructive Lung Disease stages I–II/A–B) from the Karolinska COSMIC cohort (n=116) was analysed using our nontargeted liquid chromatography–high resolution mass spectrometry metabolomics platform.Pathway analyses revealed that several altered metabolites are involved in oxidative stress. Supervised multivariate modelling showed significant classification of smokers from COPD (p=2.8×10−7). Sex stratification indicated that the separation was driven by females (p=2.4×10−7) relative to males (p=4.0×10−4). Significantly altered metabolites were confirmed quantitatively using targeted metabolomics. Multivariate modelling of targeted metabolomics data confirmed enhanced metabolic dysregulation in females with COPD (p=3.0×10−3) relative to males (p=0.10). The autotaxin products lysoPA (16:0) and lysoPA (18:2) correlated with lung function (forced expiratory volume in 1 s) in males with COPD (r=0.86; p<0.0001), but not females (r=0.44; p=0.15), potentially related to observed dysregulation of the miR-29 family in the lung.These findings highlight the role of oxidative stress in COPD, and suggest that sex-enhanced dysregulation in oxidative stress, and potentially the autotaxin–lysoPA axis, are associated with disease mechanisms and/or prevalence.
Funder
the regional agreement on medical training and clinical research (ALF) between Stockholm County Council and Karolinska Institutet
Vetenskapsrådet
Canadian Institutes of Health Research Fellowship
Karolinska Institutet and AstraZeneca Joint Research Program in Translational Science
King Gustaf V and Queen Victoria’s Freemasons Foundation
Stiftelsen för Strategisk Forskning
King Oscar II Jubilee Foundation
EU FP6 Marie Curie
Karolinska Institutet
Hjärt-Lungfonden
AFA Försäkring
VINNOVA
Publisher
European Respiratory Society (ERS)
Subject
Pulmonary and Respiratory Medicine
Cited by
77 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献