Higher Epoxyeicosatrienoic Acids in Cardiomyocytes-Specific CYP2J2 Transgenic Mice Are Associated with Improved Myocardial Remodeling

Elevated epoxyeicosatrienoic acids (EETs) are known to be cardioprotective during ischemia-reperfusion injury in cardiomyocyte-specific overexpressing cytochrome P450 2J2 (CYP2J2) transgenic (Tr) mice. Using the same Tr mice, we measured changes in cardiac and erythrocyte membranes EETs following myocardial infarction (MI) to determine if they can serve as reporters for cardiac events. Cardiac function was also assessed in Tr vs. wild-type (WT) mice in correlation with EET changes two weeks following MI. Tr mice (N = 25, 16 female, nine male) had significantly higher cardiac and EETs compared to their WT counterparts (N=25, 18 female, seven male). Total cardiac EETs in Tr mice were positively correlated with total EETs in erythrocyte membrane, but there was no correlation with EETs or in WT mice. Following MI, and EETs were elevated in the erythrocyte membrane and cardiac tissue in Tr mice, accounting for the improved cardiac outcomes observed. Tr mice showed significantly better myocardial remodeling following MI, evidenced by higher % fractional shortening, smaller infarct size, lower reactive oxygen species (ROS) formation, reduced fibrosis and apoptosis, and lower pulmonary edema. A positive correlation between total cardiac EETs and total erythrocyte membrane EETs in a Tr mouse model suggests that erythrocyte EETs may be used as predictive markers for cardiac events. All EET regioisomers displayed similar trends following acute MI; however, the magnitude of change for each regioisomer was markedly different, warranting measurement of each individually.