TY - JOUR T1 - Vascular remodelling in IPF patients and its detrimental effect on lung physiology: potential role of endothelial to mesenchymal transition (EndMT) JF - ERJ Open Research JO - erjor DO - 10.1183/23120541.00571-2021 SP - 00571-2021 AU - Archana Vijay Gaikwad AU - Wenying Lu AU - Surajit Dey AU - Prem Bhattarai AU - Collin Chia AU - Josie Larby AU - Greg Haug AU - Stephen Myers AU - Jade Jaffar AU - Glen Westall AU - Gurpreet Kaur Singhera AU - Tillie-Louise Hackett AU - James Markos AU - Mathew Suji Eapen AU - Sukhwinder Singh Sohal Y1 - 2022/01/01 UR - http://openres.ersjournals.com/content/early/2022/01/27/23120541.00571-2021.abstract N2 - Background IPF is a progressive, irreversible fibrotic interstitial lung disease. We performed size-based quantitation of pulmonary arterial remodelling in IPF, examined the role of EndMT and effects on lung physiology.Methods Resected lung tissues from 11 normal controls (NC), and 13 IPF patients, were differentially stained using the Movat Pentachrome technique. Size-based classification for pulmonary arteries was conducted in NC and IPF tissues. For each pulmonary artery, arterial size, luminal diameter, thickness of the intima, media, adventitia, and elastin deposition was quantified using Image ProPlus7.0 software. In addition, immunohistochemical staining was performed for EndMT markers and collagen.Results Large and medium size arterial numbers were significantly reduced in IPF compared to NC (p<0.0001). Intima thickness was highest in the arterial range of 200–399 μm and 600–1000 μm (p<0.0001), while medial and adventitial thickness was significant across 200–1000 μm (p<0.05) compared to NC. Medial thickness was found to significantly affect the diffusing capacity of the lungs for carbon monoxide (DLCO) (r’=−0.8, p=0.01). Total arterial elastin in IPF was higher across all arterial ranges except 100–199 μm in IPF than NC, with the greatest differences in 200–399 μm (p<0.001) and 600–1000 μm (p<0.001). Total elastin also negatively correlated with DLCO (r’=−0.63, p=0.04) in IPF. An increase in EndMT markers and collagen type I/ IV was observed.Conclusions This is the first study demonstrating size-based differences in pulmonary arteries in IPF and its detrimental effect on lung physiology. The process of EndMT might be central to these vascular remodelling changes and could be a potential novel therapeutic target.FootnotesThis 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: Mrs. Gaikwad has nothing to disclose.Conflict of interest: Dr. Lu has nothing to disclose.Conflict of interest: Mr. Dey has nothing to disclose.Conflict of interest: Mr. Bhattarai has nothing to disclose.Conflict of interest: Dr. Chia has nothing to disclose.Conflict of interest: Dr. Larby has nothing to disclose.Conflict of interest: Dr. Haug has nothing to disclose.Conflict of interest: Dr. Myers has nothing to disclose.Conflict of interest: Dr. Jaffar has nothing to disclose.Conflict of interest: Dr. Westall has nothing to disclose.Conflict of interest: Dr. Singhera has nothing to disclose.Conflict of interest: Dr. Hackett has nothing to disclose.Conflict of interest: Dr. Markos has nothing to disclose.Conflict of interest: Dr. Eapen has nothing to disclose.Conflict of interest: Dr. Sohal reports personal fees from Chiesi, outside the submitted work . ER -