Epoxyeicosatrienoesäuren

Epoxyeicosatrienoic acids (EETs) are signaling lipids produced from arachidonic acid by cytochrome P450 epoxygenases. The four main regioisomers—5,6-, 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acids—exist as different enantiomers and act locally as bioactive mediators in various tissues.

Biosynthesis and metabolism: EETs are generated when CYP epoxygenases, such as CYP2C8/9 and CYP2J2 in humans, convert arachidonic acid to epoxides. They are rapidly metabolized by soluble epoxide hydrolase (sEH) to dihydroxyeicosatrienoic acids (DHETs), which generally show reduced activity. The balance between EETs and DHETs influences their physiological effects.

Biological functions: In the vasculature, EETs promote vasodilation by opening potassium channels in smooth muscle, contributing to blood pressure regulation. They also modulate inflammation, exert anti-apoptotic and pro-angiogenic effects, and influence renal tubular transport and electrolyte handling. EETs can affect neuronal signaling and pain pathways, reflecting a broad role in organ systems.

Clinical and research context: Tissue EET levels are regulated by CYP epoxygenases and sEH; genetic and environmental factors can alter their abundance. Inhibitors of soluble epoxide hydrolase (sEH inhibitors) raise endogenous EET levels and are studied for potential cardioprotective, neuroprotective, and anti-inflammatory benefits. Conversely, the pro-angiogenic properties of EETs have complex implications for cancer biology, warranting careful evaluation.

Measurement and research use: EETs are typically quantified in biological samples by mass spectrometry. They serve as biomarkers of epoxygenase activity and as targets for pharmacological modulation in cardiovascular and inflammatory diseases.