Institute for Vascular Signalling, Centre for Molecular Medicine, Goethe University, Frankfurt am Main, Germany.
Institute for Vascular Signalling, Centre for Molecular Medicine, Goethe University, Frankfurt am Main, Germany; German Center of Cardiovascular Research (DZHK), Partner site RheinMain, Frankfurt, Germany.
Adv Pharmacol. 2023;97:327-373. doi: 10.1016/bs.apha.2022.12.004. Epub 2023 Jan 19.
The cytochrome P450 (CYP) soluble epoxide hydrolase (sEH) pathway generates a large number of biologically active epoxides and diols from a range of ω-3 and ω-6 polyunsaturated fatty acids (PUFAs). While epoxides of arachidonic acid or epoxyeicosatrienoic acids are probably the best studied of these mediators, epoxides of linoleic acid as well as the fish oils; docosahexaenoic acid and eicosapentaenoic acid have also been attributed signaling actions. Cell and tissue levels of the PUFA epoxides are largely determined by the sEH and in many cases inflammation and chronic diseases, e.g., cardiovascular disease, diabetes and Alzheimer's disease, have been associated with increased sEH expression and the accelerated conversion of PUFA epoxides to their corresponding diols. In low concentrations, the diols act to influence stem and progenitor cells as well as brown adipose tissue but in high concentrations, they tend to have pro-inflammatory and cytotoxic effects that promote disease progression. This review outlines some of the actions to the PUFA epoxides and diols in physiology and pathophysiology as well as the beneficial effects associates with sEH inhibition.
细胞色素 P450（CYP）可溶性环氧化物水解酶（sEH）途径可从多种 ω-3 和 ω-6 多不饱和脂肪酸（PUFA）中生成大量具有生物活性的环氧化物和二醇。虽然花生四烯酸或环氧二十碳三烯酸的环氧化物可能是这些介质中研究得最好的，但亚油酸的环氧化物以及鱼油中的二十二碳六烯酸和二十碳五烯酸也被认为具有信号作用。PUFA 环氧化物的细胞和组织水平在很大程度上取决于 sEH，在许多情况下，炎症和慢性疾病，如心血管疾病、糖尿病和阿尔茨海默病，与 sEH 表达增加和 PUFA 环氧化物向相应二醇的加速转化有关。在低浓度下，二醇会影响干细胞和祖细胞以及棕色脂肪组织，但在高浓度下，它们往往具有促炎和细胞毒性作用，从而促进疾病进展。本综述概述了在生理和病理生理学中 PUFA 环氧化物和二醇的一些作用，以及与 sEH 抑制相关的有益作用。
