Pharmacological inhibition of the soluble epoxide hydrolase - from mouse to man

Epoxyeicosatrienoic acids (EETs) build a family consisting of four arachidonic acid derived regioisomers that are generated by P450 epoxygenases. In the past years, growing interest in influencing EET level arose since EETs possess numerous beneficial effects in the cardiovascular system, for example, vasodilation, anti-inflammation and elicit renal and myocardial protection. Because EETs are primarily metabolized by the soluble epoxide hydrolase (sEH) and potent inhibitors of this enzyme are currently available, pharmacological sEH inhibition seems to be a feasible approach to elevate EET level in vivo. Hence, first clinical trials on sEH inhibition in man have begun. This review focuses on sEH inhibition as a novel pharmacological cardiovascular protective strategy with special regard to in vivo investigations.