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

新发现的肾素变体的心脏保护作用：N-乙酰基-D-葡萄糖胺-2-差向异构酶作为胞质肾素的靶标

• 批准号: 181630837
• 负责人: Professor Dr. Jörg Peters
• 金额: --
• 依托单位: Institut für Physiologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2010
• 资助国家: 德国
• 起止时间: 2009-12-31 至 2012-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/181630837?language=en
• 关键词: Kardioprotektive; Effekte; einer; neu; entdeckten

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.

该项目的目的是确定肾素变体保护心脏细胞免于死亡的作用机制，并检验这种肾素亚型的过度表达对心脏干细胞具有保护作用的假设。这种肾素变体代表一种胞质蛋白，可在缺血条件下延迟心肌细胞的坏死细胞死亡，并保护离体跳动心脏梗塞后的心脏免受损伤。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。关于作用机制，我们正在进一步评估肾素结合蛋白（N-乙酰基-D-葡萄糖胺2差向异构酶，NAGE）的作用以及目前未知的靶标以及肾素对细胞代谢的影响。最后，我们将研究使用腺病毒转染过度表达肾素后移植过程中诱导多能心脏干细胞的存活情况。通过这个项目，我们希望揭示胞浆肾素的保护作用，并为治疗心肌梗死和心力衰竭获得新思路。