Impact of the mitochondria-targeted antioxidant MitoQ on hypoxia-induced pulmonary hypertension.
Schermuly, Ralph T
Brandes, Ralf P
The European respiratory journal
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Pak, O., Scheibe, S., Esfandiary, A., Gierhardt, M., Sydykov, A., Logan, A., Fysikopoulos, A., et al. (2018). Impact of the mitochondria-targeted antioxidant MitoQ on hypoxia-induced pulmonary hypertension.. The European respiratory journal https://doi.org/10.1183/13993003.01024-2017
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% O2for 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.
Wellcome Trust (110159/Z/15/Z)
External DOI: https://doi.org/10.1183/13993003.01024-2017
This record's URL: https://www.repository.cam.ac.uk/handle/1810/277184