RT Journal Article
SR Electronic
T1 Vascular remodelling in idiopathic pulmonary fibrosis patients and its detrimental effect on lung physiology: potential role of endothelial-to-mesenchymal transition
JF ERJ Open Research
JO erjor
FD European Respiratory Society
SP 00571-2021
DO 10.1183/23120541.00571-2021
VO 8
IS 1
A1 Gaikwad, Archana Vijay
A1 Lu, Wenying
A1 Dey, Surajit
A1 Bhattarai, Prem
A1 Chia, Collin
A1 Larby, Josie
A1 Haug, Greg
A1 Myers, Stephen
A1 Jaffar, Jade
A1 Westall, Glen
A1 Singhera, Gurpreet Kaur
A1 Hackett, Tillie-Louise
A1 Markos, James
A1 Eapen, Mathew Suji
A1 Sohal, Sukhwinder Singh
YR 2022
UL http://openres.ersjournals.com/content/8/1/00571-2021.abstract
AB Background Idiopathic pulmonary fibrosis (IPF) is a progressive, irreversible fibrotic interstitial lung disease. We performed size-based quantitation of pulmonary arterial remodelling in IPF and examined the role of endothelial-to-mesenchymal transition (EndMT) and effects on lung physiology.Methods Resected lung tissues from 11 normal controls (NCs), 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 and adventitia, and elastin deposition were 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 NCs (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 in 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.Pulmonary arterial remodelling occurs in IPF patients, affects lung function and may exaggerate pulmonary hypertension. Endothelial-to-mesenchymal transition appears decisive with vascular changes and could be a novel therapeutic target for IPF. https://bit.ly/3GG3qBa