Epoxyeicosatrienoic Acids: Novel Mediators of Cardioprotection

Recent evidence from a number of in vitro and in vivo studies in isolated cells and animal models has suggested that the cytochrome P450 (CYP450) pathway of arachidonic acid (AA) metabolism produces potent cardioprotective metabolites that markedly reduce reversible (myocardial stunning) and irreversible (infarct size [IS]) injury in the ischemic/reperfused heart. The major players in this protective response appear to be the AA metabolites including the regioisomers of 5,6-, 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acids (EETs). The present review article will discuss the beneficial effects of the EETs on myocardial stunning and IS reduction and consider some of the signaling pathways and cellular mechanisms by which the EETs produce their beneficial effects and the possible therapeutic benefits that may result from activation of this pathway. The results discussed in this review are taken from experiments obtained from 3 diverse species in different laboratories: the mouse, rat, and dog, in which the results were nearly identical qualitatively and quantitatively, suggesting that these findings are likely to be extrapolated to man as well.