Kardioprotektive Effekte einer neu entdeckten Reninvariante: N-Acetyl-D-Glucosamin-2-Epimerase als Target für zytosolisches Renin

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Aim of the project is to determine the mechanism of action of a renin variant that protects cardiac cells from death and to test the hypothesis that overexpression of this renin isoform is protective in cardiac stem cells. This renin variant represents a cytosolic protein that delays the necrotic cell death in cardiomyocytes under ischemic conditions and protects the heart from damage after infarction in isolated beating hearts. We are now going to investigate the anti-apoptotic and anti-necrotic effects of this renin under clinical relevant ischemia related conditions and during stem cell transplantation. With respect to the mechanism of action we are further evaluating the role of renin binding protein (N-acetyl-D-glucosamine 2 epimerase, NAGE) and additionally as yet unknown targets as well as the effects of renin on cell metabolism. Finally, we are going to investigate the survival of induced pluripotent cardiac stem cells during transplantation after overexpression of renin using adenoviral transfections. With this project we hope to unravel the protective actions of cytosolic renin and gain new ideas for the treatment of cardiac infarction and cardiac failure.