Heinrich-Heine-Universität Düsseldorf

Sonderforschungsbereich 1116

Collaborative Research Center 1116 „Master switches in cardiac ischemia“
Acute myocardial infarction (AMI) is among the most frequent cardiovascular disorders in the Western world. The Comprehensive Research Center (CRC, SFB) 1116 focuses on the acute and subacute phase post AMI using preclinical approaches in standardized small and large animal models as well as clinical investigations in a multidisciplinary consortium. Aim is the identification of cardiac and systemic effector mechanisms (master switches) in the acute/subacute phase after AMI that determine the morbidity and mortality after AMI and could be used as future therapeutic targets.

AMI is the consequence of thrombotic occlusion of coronary arteries and is therefore a local cardiac event. However, the adaptation of the heart after cardiac ischemia is strongly determined by a complex crosstalk between cardiac and extracardiac cell populations, metabolic adaptation, comorbidities and ischemia-triggered systemic responses. For the development of novel therapeutic strategies it will be crucial to understand the interplay of cardiac healing responses with metabolic and systemic effector mechanisms. Because “late comers” receiving revascularization late or not all are quite frequent, the CRC 1116 will address both, responses to ischemia/reperfusion (I/R) and permanent coronary occlusion.

Project group A (intracellular and cellular effectors) will therefore investigate new cardiac effector mechanisms. Specifically mechanisms of arrythmogenesis, cardiomyocyte dysfunction, regulation of mitochondrial function and apoptosis, new posttranslational mechanisms, cardioprotective signaling, effects of acute remodeling of cardiac extracellular matrix on angiogenesis and fibroblast phenotype and underlying molecular mechanisms will be investigated. Thus project group A addresses important adaptative and maladaptative processes that are initiated in the myocardium in the acute and subacute phase post AMI.

Project group B (metabolic and systemic effectors) addresses relevant metabolic effector mechanisms and systemic crosstalk after AMI in an attempt to understand AMI as a systemic disease. To achieve this, the CRC focuses on type 2 diabetes mellitus (T2DM) and associated metabolic disorders such as non-alcoholic fatty liver, insulin resistance, prediabetes as well as effects of visceral and epicardiac adipose tissue. In addition to metabolic effector mechanisms, the contribution of immune mechanisms, clinical relevant comorbidities, such as anemia and mechanisms of remote cardiac conditioning will be analyzed.

In the long-term perspective the CRC 1116 aims to identify new targets for improving the prognosis of patients after AMI and to allow stratification of therapeutic strategies. To achieve this long-term goal it will be the focus of the first funding period to identify new master switches mainly in preclinical murine models. Subsequently experiments will be designed to increasingly acknowledge the effect of relevant comorbidities. Large animal models and clinical studies will provide insight into the translational value of the candidate mechanisms and targets.


Heinrich-Heine-Universität Düsseldorf
Sonderforschungsbereich 1116
Universitätsstraße 1
40225 Düsseldorf
Forschung & Entwicklung
Forschung & Lehre