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

心脏代谢疾病（CMD）仍然是世界范围内的第一大死亡原因。新发现的可溶性环氧化物水解酶（sEH-P）的磷酸酶活性代谢与CMD相关的脂质介质。本项目旨在确定sEH-P的生理作用，以及其抑制是否代表一种治疗CMD的新方法。拟议的网络以J. Bellien（鲁昂大学）和E. Proschak（歌德大学）为中心，他们研究大鼠中sEH-P敲入的影响，他们将致力于开发能够在啮齿动物和人类中选择性系统性和中枢性抑制sEH-P的药理学工具。在验证后，将测试这些抑制剂的影响，并与C. Guignabert （University of Paris-Sud）在相关CMD动物模型中对肺动脉高压和细胞机制方面的基因失活进行比较。Morisseau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。

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.