The phosphatase activity of soluble epoxide hydrolase as a new target in cardiometabolic diseases

可溶性环氧化物水解酶的磷酸酶活性作为心脏代谢疾病的新靶点

• 批准号: 505561502
• 负责人: Professor Dr. Eugen Proschak
• 金额: --
• 依托单位: Institut für Pharmazeutische Chemie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/505561502?language=en
• 关键词: phosphatase; activity; soluble; epoxide; hydrolase

Cardiometabolic diseases (CMD) remain the first cause of death worldwide. The newly-identified phosphatase activity of soluble epoxide hydrolase (sEH-P) metabolizes lipid mediators linked to CMD. This projects aims to determine the physiological role of sEH-P and whether its inhibition represents a new therapeutic approach to treat CMD. The proposed network is centred around J. Bellien (Rouen University) that studies the impact of sEH-P knock-in in rats and E. Proschak (Goethe University) that will pursue the development of pharmacological tools enabling selective systemic and central sEH-P inhibition in rodents and humans. After their validation, the impact of these inhibitors will be tested and compared to that of the genetic inactivation in relevant animal models of CMD, with C. Guignabert (University of Paris-Sud) for pulmonary hypertension and cellular mechanistic aspects. Dr. Morisseau (UC Davis) will provide biochemical and analytical support to this project.

心脏代谢性疾病(CMD)仍然是世界范围内的第一大死亡原因。新近发现的可溶性环氧化物水解酶(sEH-P)的磷酸酶活性可代谢与CMD相关的脂质介质。本项目旨在确定sEH-P的生理作用及其抑制是否代表了治疗CMD的一种新的治疗方法。拟议的网络以J.Bellien(鲁昂大学)和E.Proschak(歌德大学)为中心，前者研究sEH-P敲入对大鼠的影响，后者将致力于开发能够在啮齿动物和人类中选择性地全身和中枢抑制sEH-P的药理工具。验证后，这些抑制剂的影响将在CMD的相关动物模型中进行测试，并与遗传失活的影响进行比较，C.Guignabert(巴黎大学-南德分校)在肺动脉高压和细胞机制方面的影响。莫里索博士(加州大学戴维斯分校)将为该项目提供生化和分析支持。