DiscrEET regulators of homeostasis: epoxyeicosatrienoic acids, cytochrome P450 epoxygenases and vascular inflammation

Abstract

Cytochrome P450 (CYP)-derived epoxyeicosatrienoic acids (EETs) are lipid signalling molecules that elicit vasodilatation and modulate various intracellular signalling cascades. The generation of EETs by epoxygenases expressed in the vascular endothelium has been linked with endothelial cell proliferation, migration and angiogenesis. The EETs also possess anti-inflammatory properties and can attenuate monocyte infiltration. Although an increase in CYP epoxygenase expression or activity should theoretically be beneficial, many of these enzymes generate reactive oxygen species which in themselves are pro-inflammatory and promote processes that functionally antagonize those of the EETs. There is potential for selecting the anti-inflammatory actions of the EETs by preventing their metabolism by the soluble epoxide hydrolase.