Lung Fibrosis Is Linked to Increased Endothelial Cell Activation and Dysfunctional Vascular Barrier Integrity

Pulmonary fibrosis can be a fatal disease characterized by progressive lung scarring. It is still poorly understood how the pulmonary endothelium is involved in the disease pathogenesis. Differences of the pulmonary vasculature between patients and donors were analysed using transmission electron microscopy, immunohistochemistry and single-cell-RNA-sequencing. Vascular barrier resistance, endothelial-immune cell adhesion, and sensitivity to an inflammatory milieu were studied in-vitro. Integrity and activation markers were measured by ELISA in human plasma. Transmission electron microscopy demonstrated abnormally swollen endothelial cells in fibrotic lungs as compared to donors. A more intense CD31 and vWF and patchy VE-Cadherin staining in fibrotic lungs supported the presence of a dysregulated endothelium. Integrity markers CD31, VE-Cadherin, Thrombomodulin and VEGFR-2 and activation marker von-Willebrand-Factor gene expression was increased in different endothelial subpopulations (e.g. arterial, venous, gCap, aCap) in pulmonary fibrosis. This was associated with a heightened sensitivity of fibrotic endothelial cells to TNF-

• Fließer, E.
• Jandl, K.
• Lins, T.
• Birnhuber, A.
• Valzano, F.
• Kolb, D.
• Foris, V.
• Heinemann, A.
• Olschewski, H.
• Evermann, M.
• Hoetzenecker, K.
• Kreuter, M.
• Voelkel, N. F.
• Marsh, L. M.
• Wygrecka, M.
• Kwapiszewska, G.