Τίτλος:
Orotracheal treprostinil administration attenuates bleomycin-induced lung injury, vascular remodeling, and fibrosis in mice
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Pulmonary fibrosis is a progressive disease characterized by disruption of lung architecture and deregulation of the pulmonary function. Prostacyclin, a metabolite of arachidonic acid, is a potential disease mediator since it exerts anti-inflammatory and anti-fibrotic actions. We investigated the effect of treprostinil, a prostacyclin analogue, in bleomycin-induced experimental pulmonary fibrosis. Bleomycin sulfate or saline was administrated intratracheally to mice (n = 9–10/group) at day 0. Orotracheal aspiration of treprostinil or vehicle was administered daily and started 24 h prior to bleomycin challenge. Evaluation of lung pathology was performed in tissue samples and bronchoalveolar lavage fluid collected 7, 14 and 21 days after bleomycin exposure. Lung injury was achieved due to bleomycin exposure at all time points as indicated by impaired lung mechanics, pathologic lung architecture (from day 14), and cellular and protein accumulation in the alveolar space accompanied by a minor decrease in lung tissue VE-cadherin at day 14. Treprostinil preserved lung mechanics, and reduced lung inflammation, fibrosis, and vascular remodeling (day 21); reduced cellularity and protein content of bronchoalveolar lavage fluid were additionally observed with no significant effect on VE-cadherin expression. Bleomycin-induced collagen deposition was attenuated by treprostinil from day 14, while treprostinil involvement in regulating inflammatory processes appears mediated by NF-κB signaling. Overall, prophylactic administration of treprostinil, a stable prostacyclin analogue, maintained lung function, and prevented bleomycin-induced lung injury, and fibrosis, as well as vascular remodeling, a hallmark of pulmonary hypertension. This suggests potential therapeutic efficacy of treprostinil in pulmonary fibrosis and possibly in pulmonary hypertension related to chronic lung diseases. © The Author(s) 2019.
Συγγραφείς:
Nikitopoulou, I.
Manitsopoulos, N.
Kotanidou, A.
Tian, X.
Petrovic, A.
Magkou, C.
Ninou, I.
Aidinis, V.
Schermuly, R.T.
Kosanovic, D.
Orfanos, S.E.
Περιοδικό:
Pulmonary Circulation
Εκδότης:
SAGE Publications Ltd
Λέξεις-κλειδιά:
immunoglobulin enhancer binding protein; mitogen activated protein kinase; osteopontin; protein; stress activated protein kinase; synaptophysin; transcription factor RUNX2; treprostinil; vascular endothelial cadherin, adherens junction; animal experiment; animal model; animal tissue; Article; bleomycin-induced lung injury; blood vessel permeability; bronchoalveolar lavage fluid; cell count; cell infiltration; controlled study; enzyme linked immunosorbent assay; histopathology; immunohistochemistry; lung fibrosis; lung function; lung mechanics; morphometry; mouse; neutrophil count; nonhuman; protein expression; protein phosphorylation; vascular remodeling; Western blotting
DOI:
10.1177/2045894019881954
