Abstract

Background/Aim:The role of EndMT in IPF and its impact on airway pathophysiology remains unexplored. We previously reported size-based aberrant arterial remodelling in IPF and its impact on lung physiology. We now illustrate the role of EndMT in driving these changes 

Methods: Immunohistochemical staining for VE-cadherin (VCad), N-cadherin (Ncad), S100A4, and vimentin (Vn) was performed on lung resections from 13 IPF patients and 15 normal controls (NC). Junctional (Jn) and cytoplasmic (Cy) VCad+/- endothelial cell counts per mm of basement membrane were done. For S100A4, NCad and Vn, percent expression in pre-classified arteries (100-1000µm range) for total and intima, media, and adventitia was carried out. All image analyses was done using Image ProPlus7.0. 

Results: Compared to NC, cellular transition was noted in IPF arteries, with upregulated mesenchymal marker Ncad, S100A4 and Vn expression and downregulated VCad Jn+ endothelial cells. Quantitative analysis of NC showed 50% of total endothelial cells were VCad Jn+, was 20% in IPF (p <0.01), concomitantly, VCad Cy+ cells rose across all arterial ranges in IPF (p<0.01) than NC. Ncad and Vn expression were significantly higher across arterial ranges (p<0.0001 and p<0.001), while S100A was higher in small-mid-range arteries (p<0.001). Similar significant NCad and Vn expression was observed across sizes in intima, media, and adventitia. Furthermore, intimal Vn significantly affected %DLCO (r'=-0.62, p=0.04) while increase in Vn and Ncad impacted arterial thickness (r'=0.55, p=0.04 and r'=0.61, p=0.02). 

Conclusion: Our study indicated that EndMT is a crucial phenomenon in arterial remodelling and adversely impacts IPF vascular pathophysiology.