Lai Jinsheng, Chen Chen
Division of Cardiology, Tongji Hospital, Tongji Medical College and Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiologic Disorders, Huazhong University of Science and Technology, Wuhan, China.
Front Physiol. 2021 Feb 24;12:642470. doi: 10.3389/fphys.2021.642470. eCollection 2021.
Epoxyeicosatrienoic acids (EETs) are metabolites of arachidonic acid by cytochrome P450 (CYP) epoxygenases, which include four regioisomers: 5,6-EET, 8,9-EET, 11,12-EET, and 14,15-EET. Each of them possesses beneficial effects against inflammation, fibrosis, and apoptosis, which could combat cardiovascular diseases. Numerous studies have demonstrated that elevation of EETs by overexpression of CYP2J2, inhibition of sEH, or treatment with EET analogs showed protective effects in various cardiovascular diseases, including hypertension, myocardial infarction, and heart failure. As is known to all, cardiac remodeling is the major pathogenesis of cardiovascular diseases. This review will begin with the introduction of EETs and their protective effects in cardiovascular diseases. In the following, the roles of EETs in cardiac remodeling, with a particular emphasis on myocardial hypertrophy, apoptosis, fibrosis, inflammation, and angiogenesis, will be summarized. Finally, it is suggested that upregulation of EETs is a potential therapeutic strategy for cardiovascular diseases. The EET-related drug development against cardiac remodeling is also discussed, including the overexpression of CYP2J2, inhibition of sEH, and the analogs of EET.
环氧二十碳三烯酸(EETs)是花生四烯酸经细胞色素P450(CYP)环氧化酶代谢产生的产物,包括四种区域异构体:5,6-EET、8,9-EET、11,12-EET和14,15-EET。它们各自对炎症、纤维化和细胞凋亡均具有有益作用,可对抗心血管疾病。大量研究表明,通过过表达CYP2J2、抑制可溶性环氧化物水解酶(sEH)或用EET类似物治疗来提高EETs水平,在包括高血压、心肌梗死和心力衰竭在内的各种心血管疾病中均显示出保护作用。众所周知,心脏重塑是心血管疾病的主要发病机制。本综述将首先介绍EETs及其在心血管疾病中的保护作用。接下来,将总结EETs在心脏重塑中的作用,尤其着重于心肌肥大、细胞凋亡、纤维化、炎症和血管生成。最后,表明上调EETs是心血管疾病的一种潜在治疗策略。还将讨论针对心脏重塑的与EET相关的药物开发,包括CYP2J2的过表达、sEH的抑制以及EET类似物。