Abstract
Background We have previously reported arterial remodelling in patients with idiopathic pulmonary fibrosis (IPF) and suggested that endothelial to mesenchymal transition (EndMT) might be central these changes. This study aims to provide evidence for active EndMT in IPF patients.
Methods Lung resections from thirteen patients with IPF and fifteen normal controls (NC) were immunostained for EndMT biomarkers: VE-cadherin, N-cadherin, S100A4 and vimentin. Pulmonary arteries were analysed for EndMT markers by using computer and microscope assisted image analysis software Image ProPlus7.0. All the analysis was done with observer blinded to subject and diagnosis.
Results Increased expression of mesenchymal markers N-cadherin (p<0.0001), vimentin (p<0.0001), and S100A4 (p<0.05), was noted with downregulation of junctional endothelial VE-cadherin (p<0.01) in intimal layer of the arteries from patients with IPF compared to NC. Cadherin switch was observed in IPF patients, showing increase in endothelial N-cadherin and decrease in VE-cadherin (p<0.01). There was also VE-cadherin shift from junctions to cytoplasm (p<0.01), effecting endothelial cell integrity in patients with IPF. In IPF, individual mesenchymal markers vimentin and N-cadherin negatively correlated with diffusing capacity of the lungs for carbon monoxide (r'=-0.63, p=0.03 and r’=-0.66, p= 0.01). Further, N-cadherin positively correlated with arterial thickness (r'=0.58, p=0.03).
Conclusion This is the first study to demonstrate active EndMT in size based classified pulmonary arteries from IPF patients and potential role in driving remodelling changes. The mesenchymal markers had negative impact on the diffusing capacity of the lungs for carbon monoxide. This work also informs early origins of pulmonary hypertension in patients with IPF.
Footnotes
This manuscript has recently been accepted for publication in the ERJ Open Research. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJOR online. Please open or download the PDF to view this article.
Conflict of interest: Sukhwinder Singh Sohal reports personal fees for lectures from Chiesi, travel support from Chiesi and AstraZeneca, and research grant from Boehringer Ingelheim outside the submitted work.
Conflict of interest: All the other authors do not have any conflict of interest to declare.
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- Received October 3, 2022.
- Accepted January 26, 2023.
- Copyright ©The authors 2023
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