Zhang_2022_Life.Sci_310_121122

Epoxyeicosatrienoic acids (EETs) are important endogenous substances that affect heart function in human body. Animal models of cytochrome P450 (CYP) and soluble epoxide hydrolase (sEH) related cardiovascular diseases (CVD) have revealed the physiological effects of EETs, mainly including vascular function regulation, angiogenesis, myocardial fibrosis, myocardial hypertrophy, and cardiovascular inflammation. At the same time, clinical studies have found that most of the substrates and inhibitors of CYP2J2 affect the content of EETs, resulting in cardiotoxicity of drugs. Therefore, the regulation of CYP and sEH enzymes on EETs points out the direction for exploring EET-mediated cardiac protection. The metabolic pathway of EETs is not only an important target for the development of new drugs for CVD but also an important factor in preventing drug cardiotoxicity. The development and clinical application of sEH inhibitors and EETs analogues provide broad prospects for the treatment of CVD.