Role of IL-11 system in Pulmonay Hypertension

Resum

Background: Pulmonary artery hypertension (PAH) is characterised by pulmonary artery (PA) vasoconstriction and PA remodelling. Although current vasodilator improve idiopathic PAH disease, they do not modify PA hypermuscularization and have no effect on PH associated to chronic lung disease (PHCLD). IL-11 system is activated in different proliferative and fibrotic diseases. However the role of IL-11 system in PH is unknown.Objective: To study the role of IL-11 system on PH cellular processesMethods: Levels of IL-11 and soluble IL-11 receptor were measured in serum from healthy subjects, idiopathic PAH (class 1 PH), idiopathic pulmonary fibrosis (IPF) and PHCLD-IPF (class 3 PH). PA endothelial cells (EC) and PA smooth muscle cells (SMC) were stimulated with ILL-11, IL-11Rs or with the combination of IL-11+IL-11Rs. Cellular processes such as PAEC tube formation and senescence, and PASMC proliferation and migration were evaluated. In addition, PAEC and PASMC to mesenchyal transformation were evaluated by PCR and and the activation of gp130 and jak2 by western blot.Results: Serum IL-11 and IL-11Rs levels were increased in PAH (n=5) and PH-IPF patients (n=15) vs. Healthy (n=10) and IPF (n=8). IL-11 and IL-11Rs in monotherapy increased PAEC tube formation, EnMT, PASMC proliferation and migration, and synergic effects when combined. Furthermore, PAEC and PASMC to mesenchyal transformation were evaluated measuring the increase of collagen type I, PDGF and FGF expression and decrease of endothelial markers VE-cadherin, NOS3, FVIII. Finally, it was observed that IL-11+ IL-11Rs promoted the phosphorylation of gp130 and jak2 in a greater extent than IL-11 in monotherapy.Conclusions: IL-11 system could be a promising therapeutic option in PH.Footnotes Cite this article as: European Respiratory Journal 2020; 56: Suppl. 64, 1495.This abstract was presented at the 2020 ERS International Congress, in session “Respiratory viruses in the "pre COVID-19" era”.This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at [www.ers-education.org][1] (ERS member access only). [1]: http://www.ers-education.org