epoxyeicosatriekzuren

Epoxyeicosatrienoesäuren, commonly abbreviated as EETs, are signaling lipids derived from arachidonic acid through the action of cytochrome P450 epoxygenases. The most studied regioisomers are 5,6-, 8,9-, 11,12-, and 14,15-EET. These molecules are produced mainly in endothelial cells and other tissues and serve as important mediators of vascular function, inflammation, and tissue homeostasis.

Biosynthesis and metabolism

EETs are generated by cytochrome P450 epoxygenases, particularly the CYP2C and CYP2J families. They are rapidly metabolized by soluble epoxide hydrolase (sEH) to the corresponding dihydroxy derivatives (DHETs), which generally have lower biological activity. Levels of EETs can be influenced by genetic factors, diet, and disease states, and can be pharmacologically increased by sEH inhibitors.

Actions and mechanisms

EETs promote vasodilation and contribute to endothelium-derived hyperpolarization by activating potassium channels in vascular smooth muscle, leading to smooth muscle relaxation. They also modulate inflammation, apoptosis, and angiogenesis, and can have neuroprotective effects in certain contexts. Through these actions, EETs participate in the regulation of blood pressure, renal function, and tissue responses to ischemia.

Physiological and clinical relevance

In physiology, EETs help maintain vascular tone and kidney function and participate in healing after injury. In pathology, altered EET signaling has been linked to hypertension, ischemia-reperfusion injury, and cancer, where their pro-angiogenic effects can influence tumor growth. Therapeutically, inhibiting sEH to raise endogenous EET levels is an area of research for cardiovascular diseases, pain management, and inflammatory conditions.

Notes

EETs are sometimes discussed in German-language literature as Epoxyeicosatrieensäuren. Measurement of their levels typically involves specialized lipidomics methods.