RT Journal Article
SR Electronic
T1 Sildenafil inhibit dose-dependently profibrotic and remodelling effects of TGFβ1 on pulmonary arteries from patients with idiopathic pulmonary fibrosis (IPF)
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP P2341
VO 44
IS Suppl 58
A1 Gustavo Juan
A1 Javier Milara
A1 Jose Luis Ortiz
A1 Juan Escriva
A1 Mercedes Ramon
A1 Estrella Fernandez
A1 Julio Cortijo
YR 2014
UL http://erj.ersjournals.com/content/44/Suppl_58/P2341.abstract
AB Introduction: Pulmonary hypertension (PH) in IPF although included in WHO class 3 (hypoxia-associated PH), it has been postulated that shares pathogenic features with IPH.Aims. - To study the pulmonary arterial remodeling process in patients with PH complicating IPF, and how the PDE5 inhibitor sildenafil modulate this pathogenic process.Methods:Peripheral pulmonary arteries were obtained from,1) Patients with IPF with PH and without PH who underwent surgery for lung transplantation, 2) Patients with PH without IPF transplanted and 3) Controls. Endothelial and mesenchymal markers were analyzed before and after stimulated with TGFβ and inhibited with sildenafil. We have also analyzed the endothelial to mesenchymal transition induced by TGFβ1and modulated by sildenafil.Results.We observed an increase of mesenchymal/fibrotic markers in pulmonary arteries from patients with IPF and IPF +PH. By contrast endothelial markers were down-regulated. In pulmonary artery rings, from patients with IPF and in a lesser extent in controls, TGFβ1 increases mesenchymal markers while endothelial markers were down-regulated. Sildenafil dose-dependently inhibited both processes.Conclusions: 1)Mesenchymal/fibrotic markers are increased and endothelial markers were down-regulated in isolated pulmonary arteries from IPF+PH > IPF > control 2) In pulmonary artery rings cultured ex vivo and stimulated with TGFβ1, mesenchymal markers were over-expressed in IPF patients and in a lesser extent in control patients. Sildenafil, dose-dependently, inhibited profibrotic and remodelling effects of TGFβ1 on pulmonary arteries.