Project Details
Projekt
FOR 604: Signalling Pathways in the Healthy and Diseased Heart
Subject Area
Medicine
Term
from 2005 to 2012
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 13286686
Heart failure is a devastating condition with increasing prevalence and poor outcome. Heart failure is the consequence of a relevant loss of viable myocardium (e.g. after myocardial infarction), of chronic overload (e.g. in arterial hypertension) or a primary disease of the cardiac muscle (e.g. inherited cardiomyopathies or after virus infection). Clinical studies indicate that, despite the success of modern pharmacotherapy with ACE inhibitors, betablockers and aldosterone receptor blockers, the principle of neurohumoral blockade in heart failure approaches its limits and it is apparent that none of the present pharmacological principles primarily pargets biological processes in the diseased cardiac myocyte itself.
A major goal of the Research Unit is to identify new, signalling mechanisms in cardiac myocytes and better characterise known ones. Malfunction or overactivity of such signalling pathways and their molecular players could participate in the acceleration or delay of the heart failure disease progress and may therefore, on the long run, represent new targets for drug therapy.
The strength of this multidisciplinary Research Unit is the use and transfer of knowledge and technology from different areas of molecular biology and more applied biomedical fields. The projects can be broadly categorised into three thematic complexes - cardiac myocyte Ca2+ handling, cardiac rhythm and cardiac growth.
In particular, we will study by transgenic mouse technology and molecular, biochemical, pharmacological and physiological means the role of the anion exchanger AE3, new second messengers such as cyclic ADP ribose, the protein phosphatase inhibitor 1, the cardiac pacemaker channel HCN4, adrenergic regulation of potassium channels and the ubiquitin-proteasome system in isolated cardiac myocytes as well as the whole animal (mouse) under normal conditions and situation of cardiac stress and/or failure. Most of these signalling pathways are just being recognised in the cardiac field. We hope that the combined effort will open new perspectives in the treatment of heart failure.
A major goal of the Research Unit is to identify new, signalling mechanisms in cardiac myocytes and better characterise known ones. Malfunction or overactivity of such signalling pathways and their molecular players could participate in the acceleration or delay of the heart failure disease progress and may therefore, on the long run, represent new targets for drug therapy.
The strength of this multidisciplinary Research Unit is the use and transfer of knowledge and technology from different areas of molecular biology and more applied biomedical fields. The projects can be broadly categorised into three thematic complexes - cardiac myocyte Ca2+ handling, cardiac rhythm and cardiac growth.
In particular, we will study by transgenic mouse technology and molecular, biochemical, pharmacological and physiological means the role of the anion exchanger AE3, new second messengers such as cyclic ADP ribose, the protein phosphatase inhibitor 1, the cardiac pacemaker channel HCN4, adrenergic regulation of potassium channels and the ubiquitin-proteasome system in isolated cardiac myocytes as well as the whole animal (mouse) under normal conditions and situation of cardiac stress and/or failure. Most of these signalling pathways are just being recognised in the cardiac field. We hope that the combined effort will open new perspectives in the treatment of heart failure.
DFG Programme
Research Units
Projects
- Analysis of hyperpolarization-activated cyclic nucleotide-gated (HCN) channel function in adult heart using conditional transgenic mouse models (Applicant Isbrandt, Dirk )
- Animal experimentation and cardiac phenotyping of transgenic mouse models (Applicant Eschenhagen, Thomas )
- Effects and regulation of phosphatase inhibitor-1 in the heart and its therapeutic potential in heart failure (Applicant El-Armouche, Ali )
- Identification of biophysical and paracrine factors governing electrical integration of cardiomyocytes into a functional syncytium (Applicant Zimmermann, Wolfram-Hubertus )
- Investigation of cardiac ion channel modulation in mouse models (Applicant Pongs, Olaf )
- Investigation of the ubiquitin-proteasome system in the pathogenesis of familial hypertrophic cardiomyopathy (Applicant Carrier, Lucie )
- Role of AE3 and NHE1 in cardiomyocyte homeostasis and remodeling (Applicant Hübner, Christian Andreas )
- Role of Ca2+ mobilizing second messenger NAADP in local and global Ca2+ signalling in mouse cardiac myocytes (Applicant Guse, Andreas H. )
Spokesperson
Professor Dr. Thomas Eschenhagen
