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

该项目的目的是确定一种肾素变体保护心脏细胞免于死亡的作用机制，并验证这种肾素异构体在心脏干细胞中过度表达具有保护作用的假设。这种肾素变体代表了一种细胞质蛋白，它可以延缓缺血条件下心肌细胞的坏死细胞死亡，并保护离体跳动心脏梗死后的心脏免受损伤。我们现在将研究这种肾素在临床相关缺血相关条件下和干细胞移植过程中的抗凋亡和抗坏死作用。关于肾素的作用机制，我们正在进一步评估肾素结合蛋白（n -乙酰- d -葡萄糖胺2 epimerase， NAGE）和其他未知靶点的作用以及肾素对细胞代谢的影响。最后，我们将利用腺病毒转染研究肾素过表达诱导多能心脏干细胞在移植过程中的存活情况。我们希望通过本项目揭示胞质肾素的保护作用，为心肌梗死和心力衰竭的治疗提供新的思路。

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.