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 Opacic; 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

doi:10.1016/j.jacbts.2022.02.018

Right Heart Failure in Mice Upon Pressure Overload Is Promoted by Mitochondrial Oxidative Stress

JACC Basic Transl Sci. 2022 Jul 6;7(7):658-677. doi: 10.1016/j.jacbts.2022.02.018. eCollection 2022 Jul.

Authors

Marion Müller^{1

2}, Cornelius Bischof^{1

2}, Torben Kapries^{1

2}, Sophie Wollnitza^{1

2}, Chiara Liechty^{1

2}, Simon Geißen³, Torben Schubert^{1

2}, Dragan Opacic⁴, Muhammed Gerçek¹, Vera Fortmeier¹, Daniel Dumitrescu¹, Uwe Schlomann^{1

2}, Akylbek Sydykov⁵, Aleksandar Petrovic⁵, Leoni Gnatzy-Feik⁶, Hendrik Milting⁷, Ralph T Schermuly⁵, Kai Friedrichs¹, Volker Rudolph^{1

2}, Anna Klinke^{1

2}

Affiliations

¹ Clinic for General and Interventional Cardiology/Angiology, Herz- und Diabeteszentrum NRW, University Hospital of the Ruhr-Universität Bochum, Bad Oeynhausen, Germany.
² Agnes Wittenborg Institute for Translational Cardiovascular Research, Herz- und Diabeteszentrum NRW, University Hospital of the Ruhr-Universität Bochum, Bad Oeynhausen, Germany.
³ Department of Cardiology and Cologne Cardiovascular Research Center, University Hospital Cologne, Cologne, Germany.
⁴ Clinic for Thoracic and Cardiovascular Surgery, Herz- und Diabeteszentrum NRW, University Hospital of the Ruhr-Universität Bochum, Bad Oeynhausen, Germany.
⁵ Universities of Giessen and Marburg Lung Center, Excellence Cluster Cardio-Pulmonary System, Member of the German Center for Lung Research (DZL), Giessen, Germany.
⁶ Center for Molecular Medicine Cologne und Cologne Cardiovascular Research Center, University Hospital Cologne, Cologne, Germany.
⁷ Erich and Hanna Klessmann Institute, Herz- und Diabeteszentrum NRW, University Hospital of the Ruhr-Universität Bochum, Bad Oeynhausen, Germany.

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.

Keywords: 6J, C57BL/6J; 6N, C57BL/6N; NNT, nicotinamide nucleotide transhydrogenase; PAB, pulmonary artery banding; RHF, right heart failure; RVD, right ventricular dysfunction; RVH, right ventricular hypertrophy; TAPSE, tricuspid annular plane systolic excursion; iRVF, severely impaired right ventricular function; nRVF, normal right ventricular function; oxidative stress; pressure overload; pulmonary artery banding; reactive oxygen species; right heart failure.