Soluble epoxide hydrolase as a therapeutic target for cardiovascular diseases

Arachidonic acid is metabolized to epoxyeicosatrienoic acids (EETs) by cytochrome P450 epoxygenase. Four EET regioisomers, 5,6-, 8,9-, 11,12- and 14,15-EETs, are formed depending on the location of the epoxy group. EETs can function as endothelium-derived hyperpolarizing factors in many vascular beds, and they also promote angiogenesis and inhibit inflammatory processes and platelet aggregation. EETs are rapidly converted to their corresponding less bioactive diols by soluble epoxide hydrolase (sEH). Inhibition of the degradation of EETs provides protection against injuries related to vascular dysfunction, inflammation and reactive oxygen species. Therefore, sEH has been proposed as a therapeutic target in the treatment of many vascular diseases, such as hypertension, myocardial infarction, renal diseases and ischemic stroke. In this regard, several potent and selective sEH inhibitors have been developed and proven effective in experimental models of vascular diseases.