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

We have previously reported pulmonary arterial remodelling in smokers and patients with early COPD, which can be attributed to EndMT. In this study, we aimed to evaluate if EndMT is an active mechanism in smokers and COPD.Immunohistochemical staining for EndMT biomarkers, CD-31, N-cadherin, Vimentin and S100A4, was done on lung resections from 49 subjects. Fifteen were non-smoker-controls (NC), six normal lung function smokers (NLFS), nine patients with small-airway diseases (SAD), nine mild-moderate COPD-current smokers (COPD-CS) and ten COPD-ex-smokers (COPD-ES). Pulmonary arteries were analysed using Image ProPlus software v7.0.We noted reduced junctional CD31-positive endothelial cells (p<0.05) in intimal layer of all smoking groups compared to NC. Compared to NC, increased abundance of mesenchymal markers N-cadherin (p<0.05) and Vimentin (p<0.001) was observed in all smoking groups and across all arterial sizes, except for N-Cadherin in large arterial size for COPD-CS. Abundance of S100A4 correlated with arterial thickness (r= 0.29, 0.33, 0.35; p=0.05, 0.03, 0.02 respectively for small, medium, and large arteries). Vimentin in the small arterial wall negatively correlated with FEV1/ FVC and FEF25–75% (r= −0.35, −0.34; p= 0.02,0.03, respectively), while increased cytoplasmic CD-31 abundance in the intimal layer of medium and large arteries negatively correlated with DLCO-predicted (r= −0.35, −0.39; p=0.04, 0.03 respectively).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 the potential early origins of pulmonary hypertension in smokers and patients with early COPD.