Project Details
Projekt
KFO 155: The Relevance of Biomechanics and Ca2+-Metabolism in Heart Failure and Regeneration
Subject Area
Medicine
Term
from 2006 to 2014
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 18652202
The socio-economical and medical impact of congestive heart failure is profound. Despite important therapeutical advances, heart failure patients have a substantially impaired quality of life and their 5-year-mortality exceeds 50 percent. Heart failure is a systemic disease in which pump failure and arrhythmogenesis are aggravated by neuro-endocrine mechanisms. Research efforts in the area of these neuro-endocrine mechanisms have, in recent years, significantly contributed to an improvement of therapy by using pharmacological inhibitors of the renin-angiotensin-aldosterone system (RAAS) and of beta-adrenergic receptors. Current research findings suggest that further therapeutic benefit can be expected from a better understanding of the myocardial remodelling processes and regeneration mechanisms. This is within the focus of our Clinical Research Unit.
The impairment of cardiac mechanics and the generation of cardiac arrhythmias are determined by molecular remodelling processes which are predominantly mediated by altered hemodynamic loading conditions of the heart. In this context, preload refers to augmented ventricular filling and distension of the myocardial wall during diastole. Afterload, in contrast, is determined by the vascular resistance and the myocardial wall tension during systole. Irrespective of the primary cause, alterations in pre- and/or afterload cause cardiac remodelling, hypertrophy, arrhythmogenesis and failure. Following myocardial infarction, such processes occur in the non-infarcted, hemodynamically challenged remote myocardium, while during arterial hypertension, in cardiac malformation, and genetically caused heart disease they occur ubiquitously in the myocardium.
Research within the Clinical Research Unit is targeted at identifying the signal transduction mechanisms specifically triggered by pre- and afterload. Within the focus are sarcomeric Z-disc proteins and their interactions with intracellular Ca2+-dependent signalling processes.
Furthermore, we want to evaluate which myocardial regenerative processes involving stem cells are possible and how they are determined by local, especially biomechanical load-dependent factors. This work will advance our understanding of the pathophysiology of molecular myocardial remodelling and will help develop novel therapeutic approaches in heart disease.
The impairment of cardiac mechanics and the generation of cardiac arrhythmias are determined by molecular remodelling processes which are predominantly mediated by altered hemodynamic loading conditions of the heart. In this context, preload refers to augmented ventricular filling and distension of the myocardial wall during diastole. Afterload, in contrast, is determined by the vascular resistance and the myocardial wall tension during systole. Irrespective of the primary cause, alterations in pre- and/or afterload cause cardiac remodelling, hypertrophy, arrhythmogenesis and failure. Following myocardial infarction, such processes occur in the non-infarcted, hemodynamically challenged remote myocardium, while during arterial hypertension, in cardiac malformation, and genetically caused heart disease they occur ubiquitously in the myocardium.
Research within the Clinical Research Unit is targeted at identifying the signal transduction mechanisms specifically triggered by pre- and afterload. Within the focus are sarcomeric Z-disc proteins and their interactions with intracellular Ca2+-dependent signalling processes.
Furthermore, we want to evaluate which myocardial regenerative processes involving stem cells are possible and how they are determined by local, especially biomechanical load-dependent factors. This work will advance our understanding of the pathophysiology of molecular myocardial remodelling and will help develop novel therapeutic approaches in heart disease.
DFG Programme
Clinical Research Units
Projects
- Bedeutung des sarkolemmalen Natrium Kanals für kardiale Kontraktilität und Arrhythmogenese (Applicant Maier, Lars )
- Bedeutung von Angiogenese für die kardialen Umbauvorgänge bei Last-induzierter Myokardhypertrophie und Herzinsuffizienz (Applicant Schäfer, Katrin )
- Biomechanische Last als Stellgröße der kardialen Differenzierung in embryonalen mesodermalen Vorläuferzellen (Applicant Zimmermann, Wolfram-Hubertus )
- Der Einfluss mechanischer Last auf das Potential spermatogonialer Stammzellen zur kardialen und vaskulären Regeneration (Applicant Engel, Wolfgang )
- Die Bedeutung von BRCA 1-assoziiertem Protein in der Entwicklung der induzierten Myokardhypertrophie (Applicant Seidler, Tim )
- Die Bedeutung von T-cap für die myokardiale Mechanosensor-Funktion und die Entstehung einer Herzinsuffizienz (Applicant Knöll, Ralph )
- Koordination der Klinischen Forschungsgruppe 155 (Applicant Hasenfuß, Gerd )
- Lastabhängige Erregungs-Transkriptions-Kopplung im humanen Myokard (Applicant Pieske, Burkert )
- Lastabhängige Veränderung der Expression und mechanischen Funktion von Titin und Titin-Liganden im Herzmuskel (Applicant Linke, Wolfgang )
- Lastabhängigkeit der Expression Ca 2+-regulierender Proteine im Herzmuskel (Applicant Hasenfuß, Gerd )
- Lastabhängigkeit der Zellzyklusregulation - Bedeutung für die Entstehung und Therapie der Herzinsuffizienz (Applicant Hasenfuß, Gerd )
- Protektiver Effekt von HIF-1 bei erhöhter mechanischer Belastung des Herzens (Applicant Katschinski, Dörthe M. )
- Ryanodinrezeptor-Dysfunktion als Ursache von intrazellulärem Ca2+-Leck bei Herzinsuffizienz und Arrhythmien (Applicant Lehnart, Stephan E. )
Spokesperson
Professor Dr. Gerd Hasenfuß
