作者
Elisabeth Fließer,Anna Birnhuber,P. Böhm,Konrad Hötzenecker,Gabòr Kovàcs,Horst Olschewski,Grażyna Kwapiszewska
摘要
Pulmonary fibrosis (PF) shares the same features as aberrant wound healing, characterized by complex cellular and molecular alterations. Next to epithelial cells, endothelial cells (ECs) may play a key role in the pathogenesis of PF, however, detailed information on EC characteristics is missing. Here, we provide an analysis of vascular markers implicated in EC integrity and activation in PF lung tissue and plasma samples. Expression levels of the surface markers CD31/PECAM1, VE-Cadherin/CDH5, von Willebrand Factor/VWF, thrombomodulin/THBD and VEGFR-2/KDR as well as activation markers intercellular adhesion molecule 1-3/ICAM1-ICAM3, vascular cell adhesion molecule 1/VCAM1 and P-Selectin/SELP were determined in PF (n=18) and donor lung tissue (n=19) by quantitative RT-PCR. Corresponding circulating levels were determined in plasma samples from PF patients (n=18) and controls (n=29) by ELISA. Expression analysis revealed a downregulation of thrombomodulin, ICAM-2 and ICAM-3 in PF compared to control lung tissue (p=0.0500, p=0.0041, p=0.0015, respectively). In contrast, systemic levels of surface EC markers VE-Cadherin, thrombomodulin and VEGFR-2 were significantly decreased, while the activation markers ICAM-1, vWF and P-selectin were significantly increased. Soluble vWF and expression levels of CD31 and P-selectin were significantly correlated with a decrease in lung function (r=-0.39, p=0.018, r=-0.53, p=0.025, r=-0.78, p=0.04, respectively). These results suggest that a dysregulated EC compartment is associated with restrictive lung function and gas exchange impairment in PF.