Impact of elevated pre- and afterload on production of reactive oxygen species in cardiac myocytes

• Applicant: Professor Dr. Christoph Maack
• Subject Area: Cardiology, Angiology
• Term: from 2015 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 290177420

Oxidative stress plays a causal role in the pathophysiology of heart failure. Important sources of reactive oxygen species (ROS) in cardiac myocytes are mitochondria, but also NADPH oxidase (Nox2). Our previous work identified a novel mechanism how elevated cardiac afterload increases the emission of ROS from mitochondria. This mechanism involves the oxidation of NADH at the electron transport chain and the oxidation of NADPH via the reverse mode of the nicotinamide nucleotide transhydrogenase (Nnt). In contrast, the work of others suggested an activation of Nox2 in response to elevated cardiac pre- or afterload. The aim of the present project is to elucidate the consequences of elevated pre- or afterload on mitochondrial and Nox2-dependent ROS production as well as the interplay that exists between both sources. To this end, we apply a unique combination of microscopy technology (that involves force measurements on single cardiac myocytes) and transgenic technology (using novel and more specific reporters for hydrogen peroxide in mitochondria or the cytosol). The project will guide the development of specific treatments to reduce cardiac oxidative stress, which may improve cardiac function in patients with heart failure.

• DFG Programme: Research Grants
• International Connection: United Kingdom
• Cooperation Partners: Professor Dr. Tobias Dick; Professor Dr. Wolfgang Linke; Professor Ajay M. Shah