SFB 1116: Master switches in cardiac ischemia

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The fundamental and prospective aim of the CRC 1116 “Master switches in cardiac ischemia” is to identify new targets, i.e. molecules, pathways and mechanisms that are critical for the acute and subacute response to myocardial ischemia, which we define as “master switches”. Importantly, the CRC 1116 considers systemic cross talk of ischemic cardiac injury and systemic inflammatory responses, metabolic comorbidities (obesity, insulin resistance, type 2 diabetes (T2DM)) and anemia. The CRC 1116 is organized into two conceptual areas. Project group A, “Intracellular and Cellular Effectors”, will address key aspects of pathophysiologic responses to cardiac ischemia such as ion channel remodeling, sarcomere function in the remote myocardium, role of p27 and telomerase reverse transcriptase (TERT) in mitochondria, platelet functions beyond aggregation, growth factor signaling and modulators of G-protein coupled receptor signaling and their role for immune cell responses and cardiac myocyte responses, respectively, as well as in-depth analysis of the protective function of cardiac hyaluronan-rich matrix.In project group B “Metabolic Effectors and Systemic Interference” the focus lies on the complex cross talk between infarct healing and cardiac adaptation and systemic effector systems and comorbidities. The projects in project group B address (i) mechanisms regulating the inflammatory response after cardiac ischemia such as the adenosine-interleukin-6 axis and co-stimulatory molecules to modulate T cell responses (ii) mechanisms underlying the confounding effects in patients with insulin resistance, obesity and T2DM, the so far unknown role of brown adipose tissue and of sphingosine 1 phosphate in myocardial ischemia and T2DM. Potential clinical translation is expected from investigating the confounding effects of T2DM on remote ischemic conditioning in a large animal model. Using translational approaches the impact of insulin resistance, non-alcoholic fatty liver disease with ectopic lipid deposition and of T2DM in ST elevation myocardial infarction (STEMI) will be studied in patients. Thereby the CRC1116 will provide new targets (master switches) and/or treatment options taking into account the specific pathophysiological context determined by comorbidities and other systemic interferences. The identification of these “master switches” in the acute and subacute phase after cardiac ischemia will be useful to better stratify patients to targeted therapies and ultimately positively affect their long-term outcome.