Right Heart Failure in Mice Upon Pressure Overload Is Promoted by Mitochondrial Oxidative Stress
Marion Müller, Cornelius Bischof, Torben Kapries, Sophie Wollnitza, Chiara Liechty, Simon Geißen, Torben Schubert, Dragan Opačić, Muhammed Gerçek, Vera Fortmeier, Daniel Dumitrescu, Uwe Schlomann, Akylbek Sydykov, Aleksandar Petrovic, Leoni Gnatzy-Feik, Hendrik Milting, Ralph T. Schermuly, Kai Friedrichs, Volker Rudolph, Anna Klinke
Abstract
We sought to unravel pathomechanisms of the transition of maladaptive right ventricular (RV) remodeling to right heart failure (RHF) upon pressure overload. Exposure of C57BL/6J and C57BL/6N mice to pulmonary artery banding disclosed a tight relation of structural remodeling with afterload, but a dissociation from RV systolic function. Reduced release of mitochondrial reactive oxygen species in C57BL/6J mice prevented the development of RHF. In patients with left heart failure, increased oxidative damage in RV sections was associated with severely impaired RV function. In conclusion, reactive oxygen species are involved in the transition of maladaptive RV remodeling to RHF.