Molecular Mechanism of Heart Failure - Project description
Background
We are far from being able to treat the causes of heart failure in patients, let alone heal them. This is primarily because the significance of molecular, pathophysiologically relevant processes has been only inadequately reviewed in experimental models up to now. Our subproject is intended to change this and is working on selected signal cascades and key molecules and their pathophysiological significance in the regulation of hypertrophy, cell division, survival and function of cardiac muscle cells as the basis for the development of heart failure. In addition, we are working on a series of known and newly-identified secretory factors that are responsible for the communication between the different types of cells in the failing heart.
Objective
The purpose of this subproject is to utilize molecular biological research to develop prerequisites for innovative intervention strategies which can be used as the foundation for innovative treatment approaches for patients with heart failure.
Implementation
The following teams are participating in our subproject: Prof. K. Wollert at Hannover Medical School, Dr. S. Donath at the Charité Hospital of Humboldt University in Berlin, Prof. M. Böhm at the University of the Saarland, Prof. B. Pieske at the University of Goettingen, now relocated to the University of Graz, Dr. C. Zobel at the University of Cologne, and professors S. Engelhardt and J. Bauersachs at the University of Wuerzburg. These groups are currently working on messenger substances of the adrenergic system and their downstream signal molecules, including signal pathways dependent on CA2+, and the mechanisms by which these signal cascades influence the cardiac remodeling processes in heart failure. A further focal point is the functional analysis of the apoptosis repressor with caspase recruitment domain (ARC) signal molecule which regulates the survival of myocardial cells. In addition, we are studying known growth factors such as the insulin-like growth factor 1 and its significance in the development of heart failure. With the aid of gene expression analyses and yeast signal peptide trap screens, we are also searching for previously unknown secretory factors that could be used as treatments and/or biomarkers for patients with heart failure.
Added value via networking
With regard to validity, each individual model has certain limitations. It is therefore useful to examine the pathophysiological relevance of identified factors and signal molecules not only in one but in several complementary model systems. The consortium of work groups involved in the subproject „Molecular Mechanisms of Heart Failure“ offers outstanding opportunities to do so. Added value should also be achieved by the vertical networking with other clinical subprojects to accelerate the process of integrating knowledge gained from basic research in the design of clinical studies as well as the reverse process of taking knowledge from the clinic into the laboratory.