Arterial remodelling in patients with idiopathic pulmonary fibrosis (IPF) and the possible role of endothelial to mesenchymal transition (EndMT)

Aim: To perform a comprehensive quantitative analysis of pulmonary arterial changes in IPF. Methods: Movat’s Pentachrome staining was conducted on lung tissue from patients with IPF (n=13) and healthy controls (HC; n=11). Based on position and size pulmonary arteries (PA) from IPF and HC were grouped (100-199µm, 200-299µm, 300-399µm, 400-599µm and >600-1000µm). The total arterial to luminal length ratio was calculated. We measured total arterial thickness, individual arterial layer (intima, media, and adventitia) thickness, and elastin. Immunohistochemical staining for EndMT markers S100A4 and Vimentin was conducted. Tissue was quantified by using Image ProPlus 7.0 software. Results: Significant differences were apparent across all arterial sizes in IPF (p<0.0001). Intima thickness was highest in the arterial range of 200-399μm and >600<1000μm (p< 0.0001) while medial and adventitial thickness was significant across all ranges (p<0.05) compared to HC. Medial thickness was found to significantly affect DLCO (r’=-0.8, p=0.01). Total arterial elastin in IPF was higher across all arterial ranges in IPF compared to HC with the greatest differences in 200-399μm and >600<1000μm (p<0.0001). Elastin in arterial layers was found to be significantly higher in the arterial range 200-399μm size (p<0.001). Total elastin also negatively correlated with DLCO (r’=-0.63, p=0.04) in IPF. An increase in mesenchymal makers S100A4 and Vimentin was observed in all arterial layers of IPF compared to HC. Conclusion: We observed substantial vascular remodelling in IPF and its detrimental impact on lung physiology. EndMT appears decisive in these vascular changes.