RT Journal Article
SR Electronic
T1 Impact of the mitochondria-targeted antioxidant MitoQ on hypoxia-induced pulmonary hypertension
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP 1701024
DO 10.1183/13993003.01024-2017
A1 Oleg Pak
A1 Susan Scheibe
A1 Azadeh Esfandiary
A1 Mareike Gierhardt
A1 Akylbek Sydykov
A1 Angela Logan
A1 Athanasios Fysikopoulos
A1 Florian Veit
A1 Matthias Hecker
A1 Florian Kroschel
A1 Karin Quanz
A1 Alexandra Erb
A1 Katharina Schäfer
A1 Mirja Fassbinder
A1 Nasim Alebrahimdehkordi
A1 Hossein A. Ghofrani
A1 Ralph T. Schermuly
A1 Ralf P. Brandes
A1 Werner Seeger
A1 Michael P. Murphy
A1 Norbert Weissmann
A1 Natascha Sommer
YR 2018
UL http://erj.ersjournals.com/content/early/2018/01/05/13993003.01024-2017.abstract
AB Increased mitochondrial reactive oxygen species (ROS), particularly superoxide have been suggested to mediate hypoxic pulmonary vasoconstriction (HPV), chronic hypoxia-induced pulmonary hypertension (PH) and right ventricular (RV) remodelling.We determined ROS in acute, chronic hypoxia and investigated the effect of the mitochondria-targeted antioxidant MitoQ under these conditions.The effect of MitoQ or its inactive carrier substance, decyltriphenylphosphonium (TPP+), on acute HPV (1% O2 for 10 minutes) was investigated in isolated blood-free perfused mouse lungs. Mice exposed for 4 weeks to chronic hypoxia (10% O2) or after banding of the main pulmonary artery (PAB) were treated with MitoQ or TPP+ (50 mg/kg/day).Total cellular superoxide and mitochondrial ROS levels were increased in pulmonary artery smooth muscle cells (PASMC), but decreased in pulmonary fibroblasts in acute hypoxia. MitoQ significantly inhibited HPV and acute hypoxia-induced rise in superoxide concentration. ROS was decreased in PASMC, while it increased in the RV after chronic hypoxia. Correspondingly, MitoQ did not affect the development of chronic hypoxia-induced PH, but attenuated RV remodelling after chronic hypoxia as well as after PAB.Increased mitochondrial ROS of PASMC mediate acute HPV, but not chronic hypoxia-induced PH. MitoQ may be beneficial under conditions of exaggerated acute HPV.The mitochondria-targeted antioxidant MitoQ attenuates acute HPV, and RV remodelling, but not chronic hypoxia-induced PHFootnotesThis manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.