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          Institute: MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut)     Collection: Yearbook 2016     Display Documents



ID: 723975.0, MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut) / Yearbook 2016
Chymase: a multifunctional player in pulmonary hypertension associated with lung fibrosis
Authors:Kosanovic, D.; Luitel, H.; Dahal, B. K.; Cornitescu, T.; Janssen, W.; Danser, A. H.; Garrelds, I. M.; De Mey, J. G.; Fazzi, G.; Schiffers, P.; Iglarz, M.; Fischli, W.; Ghofrani, H. A.; Weissmann, N.; Grimminger, F.; Seeger, W.; Reiss, I.; Schermuly, R. T.
Date of Publication (YYYY-MM-DD):2015-10
Title of Journal:Eur Respir J
Volume:46
Issue / Number:4
Start Page:1084
End Page:1094
Audience:Not Specified
Abstract / Description: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 beta1 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.
External Publication Status:published
Document Type:Article
Communicated by:n.n.
Affiliations:MPI für physiologische und klinische Forschung
External Affiliations:Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research, Giessen, Germany. Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research, Giessen, Germany Risk Factor Modification Centre (RFMC), St. Michael's Hospital, Toronto, ON, Canada. Dept of Pharmacology, Erasmus University Rotterdam, Rotterdam, The Netherlands. Dept of Cardiovascular and Renal Research, University of Southern Denmark, Odense, Denmark Dept of Pharmacology, Maastricht University, Maastricht, The Netherlands. Dept of Pharmacology, Maastricht University, Maastricht, The Netherlands. Actelion Pharmaceuticals Ltd, Allschwill, Switzerland. Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research, Giessen, Germany Max-Planck-Institute for Heart and Lung Research, Member of the German Center for Lung Research, Bad Nauheim, Germany. Division of Neonatology, Erasmus MC Sophia Children's Hospital, Rotterdam, The Netherlands Both authors contributed equally. Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research, Giessen, Germany Both authors contributed equally ralph.schermuly@innere.med.uni-giessen.de.
Identifiers:ISSN:1399-3003 (Electronic) 0903-1936 (Linking) %R 10.1183/09031936.00018215
URL:http://www.ncbi.nlm.nih.gov/pubmed/26113671
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