Potential drivers of EndMT in pulmonary arteries of patients with early COPD

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Introduction/Aim: Pulmonary arterial remodelling and active endothelial-mesenchymal transition (EndMT) were previously reported in smokers and patients with early COPD by our research group. Here, we aim to evaluate the role of the drivers of EndMT. Methods: Surgically resected lung tissue was immunohistochemically stained for EndMT drivers, TGF-β1, pSMAD-2/3, SMAD-7, and β-catenin. We had tissue from non-smoker-controls (NC, 12), normal lung function smokers (NLFS, 6), patients with small-airway diseases (SAD, 9), mild-moderate COPD current smokers (COPD-CS, 9) and ex-smokers (COPD-ES, 10). Histopathological measurements were done using Image-Pro Plus software 7.0. Results: TGF-β1 expression in all smoking groups was lower than in the NC (p<0.05). Across arterial sizes, smoking groups showed significantly higher pSMAD-2/3 and SMAD-7 expression (p <0.05) in total and individual arterial layer than in the NC. The ratio of SAMD-7 to pSMAD-2/3 was higher in COPD patients compared to NC. β-catenin expression was significantly higher in smoking groups across arterial sizes (p <0.05), except for COPD-ES and NLFS groups in small and medium arteries, respectively. Increased β-catenin positively correlated with S100A4 in small and medium arteries (r= 0.35, 0.50; p=0.02, 0.01, respectively), with vimentin in medium arteries (r=0.42, p=0.07), and with arterial thickness of medium and large arteries (r= 0.34, 0.41, p=0.02, 0.01, respectively). Conclusion: This is the first study uncovering endothelial SMAD pathway independent of TGF-β1 in early COPD patients. Increased expression of β-catenin indicates its potential interaction with the SMAD pathway; further research is needed to identify the deviation from this classical pathway.

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