RT Journal Article
SR Electronic
T1 Chymase: a multifunctional player in pulmonary hypertension associated with lung fibrosis
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP ERJ-00182-2015
DO 10.1183/09031936.00018215
A1 Djuro Kosanovic
A1 Himal Luitel
A1 Bhola Kumar Dahal
A1 Teodora Cornitescu
A1 Wiebke Janssen
A1 A.H. Jan Danser
A1 Ingrid M. Garrelds
A1 Jo G.R. De Mey
A1 Gregorio Fazzi
A1 Paul Schiffers
A1 Marc Iglarz
A1 Walter Fischli
A1 Hossein Ardeschir Ghofrani
A1 Norbert Weissmann
A1 Friedrich Grimminger
A1 Werner Seeger
A1 Irwin Reiss
A1 Ralph Theo Schermuly
YR 2015
UL http://erj.ersjournals.com/content/early/2015/06/24/09031936.00018215.abstract
AB Limited literature sources implicate mast-cell mediator chymase in the pathologies of pulmonary hypertension and pulmonary fibrosis. However, there is no evidence on the contribution of chymase to the development of pulmonary hypertension associated with lung fibrosis, which is an important medical condition linked with increased mortality of patients who already suffer from a life-threatening interstitial lung disease.The aim of this study was to investigate the role of chymase in this particular pulmonary hypertension form, by using a bleomycin-induced pulmonary hypertension model.Chymase inhibition resulted in attenuation of pulmonary hypertension and pulmonary fibrosis, as evident from improved haemodynamics, decreased right ventricular remodelling/hypertrophy, pulmonary vascular remodelling and lung fibrosis. These beneficial effects were associated with a strong tendency of reduction in mast cell number and activity, and significantly diminished chymase expression levels. Mechanistically, chymase inhibition led to attenuation of transforming growth factor β1 and matrix-metalloproteinase-2 contents in the lungs. Furthermore, chymase inhibition prevented big endothelin-1-induced vasoconstriction of the pulmonary arteries.Therefore, chymase plays a role in the pathogenesis of pulmonary hypertension associated with pulmonary fibrosis and may represent a promising therapeutic target. In addition, this study may provide valuable insights on the contribution of chymase in the pulmonary hypertension context, in general, regardless of the pulmonary hypertension form.Chymase plays an important role in pathology of pulmonary hypertension associated with lung fibrosis http://ow.ly/MVYW6