Abstract 18792: Treatment With an EET Agonist in a Post Myocardial Infarction Model Increases Left Ventricular Ejection Fraction and Attenuates Cardiac Remodeling by Induction of HMOX1
Rationale: Myocardial Infarction (MI) leads to a progressive decline in cardiac function, an increase in patient morbidity and is an event expanding burden on the health care system. Failure of myocardial regeneration, insufficient blood flow and enhanced oxidative stress all contribute to this pathological outcome.
Objective: Since epoxyeicosatrienoic acids (EETs) agonists increase angiogenesis and vasodilation in ischemic heart, we examined if cross talk between EET and heme oxygenase-1(HMOX1) could reduce post infarcted cardiac remodeling resulting in an improvement of cardiac function in a model of post-MI.
Methods: C57B16 mice were divided into 4 groups: sham, mice with myocardial infarction (MI) via LAD ligation and mice with MI treated with an EET-agonist (NUDSA) with and without the HO activity inhibitor stannous mesoporphyrin (SnMP). NUDSA was administered 5 days after MI for 30 days (0.5 mg/kg). Myocardial echocardiography was performed to assess blood volume, velocity, LVend-diastolic and ejection fractions. Microvessel density, inflammation and pericardial fibrosis were compared among the groups.
Results: Echocardiography showed that left ventricle dilatation, measured as end diastolic area (EDA), was reduced in the NUDSA treated group compared to the MI group (EDA: MI: 0.314 ±0.01 cm2; MI+NUDSA: 0.193±0.02 cm2; p<0.01). Cardiac Index, decreased by MI, was restored by NUDSA. NUDSA treatment increased serum adiponectin levels and decreased IL-6 and MCP-1 levels (p<0.05 vs. MI), reduced fibrosis in the peri-infarct myocardium and decreased apoptosis. Immunoblot analysis of cardiac tissue demonstrated increased expression of HMOX1, VEGF and FGF along with decreased expression of TXA2 and 3NT in mice treated with NUDSA as compared to the MI group (p<0.02). All these beneficial effects were reversed by SnMP.
Conclusion: This study demonstrates that cross talk between EET and HMOX1 ameliorates cardiac remodeling in the post infarcted myocardium and increases angiogenesis, suggesting EET as a potential therapeutic strategy in the preservation of cardiac function in this animal model of post MI.
- © 2013 by American Heart Association, Inc.