Vascular remodelling in idiopathic pulmonary fibrosis patients and its detrimental effect on lung physiology: potential role of endothelial-to-mesenchymal transition

Abstract

BackgroundIPF 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.MethodsResected 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.ResultsLarge 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.ConclusionsThis 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.

Single cell meta-analysis of EndMT and EMT state in COVID-19

“…Archana et al. have shown that EndMT markers(N-cadherin, S100A4, and vimentin) are increased in the arterial layers (intima, media, and adventitia) of IPF patients ( 33 ). Similarly, during the EndMT process, active ECs express adhesion molecules, such as intercellular adhesion molecule-1 ( ICAM-1 ) and vascular cell adhesion molecule-1 ( VCAM-1 ), which enhance EndMT formation in our results.…”

Arterial remodelling in smokers and in patients with small airway disease and COPD: implications for lung physiology and early origins of pulmonary hypertension

“…Movat's pentachrome staining was performed in tissue sections from all groups following our previously published work [ 21 ].…”

“…First, maximum external diameter (end to end of adventitia) and luminal diameter (end to end of inner intima) were measured ( figure 1a ). Next, arteries with a maximum diameter between 100 µm and 1000 µm were segregated into three groups, with arteries measuring 100–299 µm classed as small, 300–499 µm as medium and 500–999 µm as large ( figure 1b ) [ 14 , 21 ].…”

“…We obtained non-overlapping images from the tissue section of each subject, consisting of arterial range 100–1000 µm. Arterial counts for all ranges along with the parenchymal tissue density calculations for each tissue section were done using a similar strategy as previously reported [ 21 ]. In brief, the absolute arterial numbers were first estimated for each tissue section by manual counting.…”

Therapeutic Modalities for Asthma, COPD, and Pathogenesis of COVID-19: Insights from the Special Issue

“…Hybrid EMT has also been suggested in COPD and patients with IPF [ 52 ]. Endothelial-to-mesenchymal transition (EndMT) is a similar process to EMT, and these drugs may have similar effects on EndMT as well, but further work is warranted [ 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 ]. Oral corticosteroids are yet to be tested for their efficacy for such effects.…”