Epoxyeicosatrienoic acids (EETs) are products of cytocrome P450
epoxygenases that have vasodilatory properties similar to endotheilum-derived hyperpolarizing
factor (EDHF). The cytochrome P450 isoform CYP2J2 was cloned and identified as
a source of EETs in human endothelial cells. Physiological concentrations of EETs
or overexpression of CYP2J2 decreased cytolcine-induced endothelial cell adhesion
molecule expression and prevented subsequent leukocyte adhesion to the vascular
wall by a mechanism involving inhibition of transcription factor NF-B and
IB kinase (IKK). The inhibitory effects of EETs were independent of their
membrane hyporpolarizing effects suggesting that these molecules play an important
non-vasodilatory role in vascular inflammation.