epoxyeicosatrienoic

Epoxyeicosatrienoic acids, or EETs, are signaling lipids derived from arachidonic acid through the action of cytochrome P450 epoxygenases. The four principal regioisomers are 5,6-, 8,9-, 11,12-, and 14,15-EET. They are short-lived mediators that function as autocrine and paracrine signals in various tissues, influencing vascular, renal, neural, and inflammatory processes.

Biosynthesis and metabolism occur when arachidonic acid is converted by CYP epoxygenases, notably from the CYP2C and CYP2J families, into epoxides (EETs). Soluble epoxide hydrolase (sEH), encoded by the EPHX2 gene, rapidly converts EETs to dihydroxyeicosatrienoic acids (DHETs), which generally have reduced biological activity. EETs can exist in freely circulating form, be esterified in phospholipids, or be carried by albumin and lipoproteins. Production of specific regioisomers varies by tissue and enzyme expression, and both genetic and pharmacological factors can influence their levels.

Physiologically, EETs promote vasodilation in many vascular beds by activating large-conductance calcium-activated potassium channels in vascular smooth muscle, leading to hyperpolarization and relaxation. They also participate in anti-inflammatory signaling, modulate renal tubular function, and can support angiogenesis and tissue protection during ischemic stress. In the central nervous system, they contribute to neurovascular coupling and other signaling pathways. The exact effects can differ among the regioisomers and biological contexts.

Clinically, attention centers on manipulating EET levels, such as with sEH inhibitors, which raise endogenous EETs and are explored for cardiovascular, pain, and inflammatory indications. EETs and their metabolites are measured in research settings using analytical methods like LC-MS/MS to assess epoxygenase activity and lipid signaling status.