Epoxyeicosatrienoic acids: formation, metabolism and potential role in tissue physiology and pathophysiology

Abstract

Background: CYP enzymes from the CYP2C and CYP2J subfamilies metabolize arachidonic acid in a regiospecific and stereoselective manner to eight epoxyeicosatrienoic acids (EETs). Various EETs have been detected in the liver, as well as in many extrahepatic tissues, and have been implicated in numerous physiological functions from cell signaling to vasodilation and angiogenesis. Objective: This report reviews the sites of expression and activity of arachidonic acid epoxygenase CYP isoforms, as well as the physiological role and metabolism of EETs in various extrahepatic tissues. Possible functions of EETs in tissue pathophysiology and implications as potential drug targets are also discussed. Methods: The most recent primary research literature on EET forming enzymes and the new physiological functions of EETs in various tissues were reviewed. Results/conclusions: Epoxyeicosatrienoic acids are important in maintaining the homeostasis and in responding to stress in various extra hepatic tissues. It is not clear whether these effects are owing to EETs acting on a universal receptor or through a mechanism involving a second messenger. A better understanding of the regulation of EET levels and their mechanism of action on various receptors will accelerate research aiming at developing therapeutic agents that target EET formation or metabolism pathways.