Jiang Shan, Han Siyi, Wang Dao Wen
Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Wuhan, China.
Front Pharmacol. 2024 Apr 2;15:1358256. doi: 10.3389/fphar.2024.1358256. eCollection 2024.
Arachidonic acid (AA) has three main metabolic pathways: the cycloxygenases (COXs) pathway, the lipoxygenases (LOXs) pathway, and the cytochrome P450s (CYPs) pathway. AA produces epoxyeicosatrienoic acids (EETs) through the CYPs pathway. EETs are very unstable and can be degraded in seconds to minutes. EETs have multiple degradation pathways, but are mainly degraded in the presence of soluble epoxide hydrolase (sEH). sEH is an enzyme of bifunctional nature, and current research focuses on the activity of its C-terminal epoxide hydrolase (sEH-H), which hydrolyzes the EETs to the corresponding inactive or low activity diol. Previous studies have reported that EETs have cardiovascular protective effects, and the activity of sEH-H plays a role by degrading EETs and inhibiting their protective effects. The activity of sEH-H plays a different role in different cells, such as inhibiting endothelial cell proliferation and migration, but promoting vascular smooth muscle cell proliferation and migration. Therefore, it is of interest whether the activity of sEH-H is involved in the initiation and progression of cardiovascular diseases by affecting the function of different cells through EETs.
花生四烯酸（AA）有三条主要代谢途径：环氧化酶（COXs）途径、脂氧化酶（LOXs）途径和细胞色素P450s（CYPs）途径。AA通过CYPs途径产生环氧二十碳三烯酸（EETs）。EETs非常不稳定，可在数秒到数分钟内降解。EETs有多种降解途径，但主要在可溶性环氧化物水解酶（sEH）存在的情况下降解。sEH是一种具有双功能性质的酶，目前的研究集中在其C末端环氧化物水解酶（sEH-H）的活性上，该酶将EETs水解为相应的无活性或低活性二醇。先前的研究报道EETs具有心血管保护作用，而sEH-H的活性通过降解EETs并抑制其保护作用来发挥作用。sEH-H的活性在不同细胞中发挥不同作用，如抑制内皮细胞增殖和迁移，但促进血管平滑肌细胞增殖和迁移。因此，sEH-H的活性是否通过EETs影响不同细胞的功能而参与心血管疾病的发生和发展，这一点值得关注。
