Abstract
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.
Highlights
Congestive heart failure (CHF) is a leading cause of morbidity and mortality that created major healthcare and economic burden in the Western world
From the second week post-myocardial infarction (MI), weight gain occurred in the groups subjected to ischemia, and by the end of the study protocol body weight (BW) was similar among all groups (Figure 2A)
Cardio-protective actions for Epoxyeicosatrienoic acids (EETs)-B were associated with diminished CHF-induced lung edema, reduced myocardial fibrosis, decreased monocytes/macrophages infiltration in the ischemic area, and increased heme oxygenase-1 (HO-1) immunopositivity in viable cardiomyocytes after MI
Summary
Congestive heart failure (CHF) is a leading cause of morbidity and mortality that created major healthcare and economic burden in the Western world. CHF is the irreversible and final consequence of a variety of etiologies; a predominant cause is coronary heart disease [1] Several factors such as hypertension, diabetes mellitus or obesity contribute to CHF development and progression as well as organ damage to lung and kidneys. The main limitation for EETs as a therapeutic application is their short half-life due to EETs being quickly converted to biologically inactive dihydroxyeicosatrienoic acids (DHETs) by the enzyme soluble epoxide hydrolase (sEH). Considering these facts, it is conceivable that any effective EETs therapeutic utilization for cardiovascular diseases can only be achieved by two major approaches
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