Epoxyeicosatrienoic acid analog EET-B attenuates post-myocardial infarction remodeling in spontaneously hypertensive rats

Epoxyeicosatrienoic acids (EETs) and their synthetic analogs have cardiovascular protective effects. Here, we investigated the action of a novel EET analog EET-B on the progression of post-myocardial infarction (MI) heart failure in spontaneously hypertensive rats (SHR). Adult male SHR were divided into vehicle- and EET-B (10 mg/kg/day; p.o., 9 weeks)-treated groups. After two weeks of treatment, rats were subjected to 30-min left coronary artery occlusion or sham operation. Systolic blood pressure and echocardiography measurements were performed at the beginning of study, 4 days before, and 7 weeks after MI. At the end of the study, tissue samples were collected for histological and biochemical analyses. We demonstrated that EET-B treatment did not affect blood pressure and cardiac parameters in SHR prior to MI. MI was induced and cardiac parameters were measured 7 weeks later. Fractional shortening (FS) was decreased to 18.4±1.0% in vehicle-treated MI rats compared with corresponding sham (30.6±1.0%) 7 weeks following MI induction. In infarcted SHR hearts, EET-B treatment improved FS (23.7±0.7%), markedly increased heme oxygenase-1 immunopositivity in cardiomyocytes and reduced cardiac inflammation and fibrosis (by 13% and 19%, respectively). In conclusion, these findings suggest that EET analog EET-B has beneficial therapeutic actions to reduce cardiac remodeling in SHR subjected to MI.