Epoxyeicosatrienoic acid (EET)

Epoxyeicosatrienoic acids (EETs) are a family of endogenous lipid signaling molecules derived from arachidonic acid by the action of cytochrome P450 epoxygenases, most notably the CYP2C and CYP2J subfamilies. There are four primary regioisomers (5,6-EET, 8,9-EET, 11,12-EET, 14,15-EET), each produced by epoxidation at specific double bonds. EETs act as autocrine and paracrine mediators, exerting vasodilatory, anti-inflammatory, and cardioprotective effects, including lowering blood pressure, inhibiting vascular inflammation, regulating endothelial function, and facilitating angiogenesis. They are rapidly metabolized by soluble epoxide hydrolase (sEH) to much less active dihydroxyeicosatrienoic acids (DHETs). EETs' beneficial actions are of significant therapeutic interest, particularly regarding cardiovascular and inflammatory diseases. However, despite extensive evidence for cell-surface EET activity, no specific high-affinity EET receptor has been conclusively identified, which limits their classification as a “therapeutic target” in the conventional sense (e.g., receptor, enzyme). Current therapeutic efforts focus on manipulating EET levels, mainly by inhibiting sEH, to enhance beneficial effects for a range of diseases including cardiovascular and renal disorders, as well as inflammation-driven pathologies.

Other names

EETEpoxyeicosatrienoic acids5,6-Epoxyeicosatrienoic acid8,9-Epoxyeicosatrienoic acid11,12-Epoxyeicosatrienoic acid14,15-Epoxyeicosatrienoic acidEpETrE

Enhancement of endogenous EET action by inhibiting soluble epoxide hydrolase (sEH), increasing EET levels and thereby their anti-inflammatory and vasodilatory effects