Deutsches Zentrum für Herzinsuffizienz Würzburg
Comprehensive Heart Failure Center

Am Schwarzenberg 15
Haus A15
97078 Würzburg

Telefon der Herzinsuffizienzambulanz:
(+49)931-201-46300/-01
Fax: (+49)931-201-646333
E-Mail: dzhi@ukw.de

Telefon der Geschäftsstelle:
(+49)931-201-46333

BMBF Förderkennzeichen:
bis 1.11.15: 01EO1004
ab  1.11.15: 01EO1504

Welcome to the Department of Translational Science

Christoph Maack, Director of the Department of Translational Science
Prof. Dr. med. Christoph Maack, Director of the Department of Translational Science

The current treatment of patients with heart failure relies mostly on blocking the effects of neuroendocrine activation, i.e., the renin-angiotensin-aldosterone system (RAAS) and the sympathetic nervous system, on the heart. While these treatments with ACE-inhibitors, β-blockers and aldosterone antagonists (and others) have improved the prognosis of patients with systolic heart failure, their mortality is still unacceptably high. Furthermore, the optimal treatment of patients with diastolic heart failure is still unclear, and no pharmacological treatment has improved the prognosis of patients with acute heart failure and/or cardiogenic shock so far. Therefore, novel therapeutic concepts are needed that go beyond the current prevailing concepts. 

The Department of Translational Science and investigates the pathomechanisms of heart failure and potential therapeutic strategies to prevent the development or ameliorate the course of the disease. In patients with heart failure, defects in excitation-contraction (EC) coupling (i.e., cardiac myocyte calcium handling and the ensuing activation of the myofilaments to induce contraction and relaxation), oxidative stress and an energetic deficit have been observed. While these processes can be analysed separately, they are yet tightly interdependent, and therefore we address these pathologies with integrative mechanistic and experimental approaches. 

A strong focus of our work lies on the interplay between EC coupling and mitochondrial energetics. In this context, the generation of reactive oxygen species (ROS) in mitochondria and its regulation through ion handling and the mitochondrial redox state are of particular importance, since ROS may play a causal role for contractile dysfunction, arrhythmias, cell death and cardiac remodelling during heart failure. We have identified several mechanisms how pathological changes in EC coupling cause oxidative stress from mitochondria that contribute to heart failure development. Furthermore, we investigate novel therapeutic concepts that target mitochondria and/or EC coupling and therefore, go beyond the current therapeutic concept of antagonising the neuroendocrine activation in patients with heart failure.

To address these topics, we employ a broad range of experimental techniques that cover the analysis of physiological and pathological processes on a subcellular (i.e., organelle), cellular, organ-wide and systemic (in vivo) level. We have a special expertise in analysing isolated cardiac myocytes using fluorescence microscopy combined with either electrical field stimulation, the patch-clamp technique or the application of force measurements in single cardiac myocytes. These approaches are important since the regulation of mitochondrial function needs to be analysed when mitochondria are embedded in their natural environment of the cell (maintaining important microdomains of regulatory factors, such as calcium and ADP) and the cells are exposed to physiological or pathological levels of workload. Furthermore, we also analyse isolated mitochondria to determine respiration, redox state and ROS formation. By combining these techniques with genetically modified animal models, we expand our concepts to the whole organ and in vivo level to understand the systemic relevance of our findings.

Our experimental platforms are organised as Core Facilities for Cellular Electrophysiology (Head: Michael Kohlhaas, PhD) and Mitochondrial Energetics (Head: Alexander Nickel, PhD).

Director

Prof. Dr. Christoph Maack
Director of Translational Research
Comprehensive Heart Failure Center
University Clinic Würzburg

Tel. +49-(0)931-201-46502 or -46333
Fax. +49-(0)931-201-646502
Maack_C@ukw.de