Abstract 12493: Eicosapentaenoic Acid Preserves Mitochondrial Fusion Ptotein OPA-1 and Oxidative Phosphorylation in Failing Myocardium after Myocardial Infarction
Introduction Eicosapentaenoic acid (EPA) is known to improve morbidity and mortality in patients with heart failure. Mitochondria is a major contributor to energy metabolism as well as programmed myocytes death, so the preservation of its function is critical in failing heart. Recently, there is a growing recognition that mitochondrial dynamics, such as fusion and fission, has a pivotal role in regulating mitochondrial function. We examined whether EPA mediates mitochondrial dynamics and function, leading to the attenuation of cardiac remodeling after myocardial infarction (MI).
Methods and Results Anterior MI was produced in male rats by ligating the left anterior descending coronary artery (MI group). In the EPA-treated group, EPA (1,000 mg/kg/day) was administrated for 12 weeks after coronary ligation (MI+EPA group). At 12 weeks after MI, echocardiography was performed to assess cardiac function. EPA improved %fractional shortening (MI:17.1±1.3% vs. MI+EPA 22.1±1.3%, p<0.05) and reduced left ventricular end-diastolic diameter (MI:9.27±0.21 mm vs. MI+EPA 8.61±0.12 mm, p<0.05). Histological examination showed EPA significantly suppressed myocyte hypertrophy and interstitial fibrosis in non-infarcted myocardium by 15% and 30%, respectively. Contents of high-energy phosphate (HEP) in cardiac tissue were measured by high-performance liquid chromatography and mitochondrial oxidative phosphorylation was assessed by O2 consumption using isolated mitochondria. After MI, HEP contents in non-infarcted myocardium were significantly reduced, and mitochondrial complex II, III, and IV activities were also impaired, while EPA treatment significantly preserved mitochondrial complex activities and HEP contents. Furthermore, MI decreased optic atrophy-1 (OPA-1) protein, a mitochondrial fusion protein, without effect on dynamin-related protein-1 (Drp-1) protein, a mitochondrial fission protein. EPA preserved OPA-1 protein, suggesting that the promotion of mitochondrial fusion might attenuate mitochondrial damage.
Conclusion These results suggest that EPA preserves mitochondrial fusion protein OPA1 and function of oxidative phosphorylation, leading to the attenuation of left ventricular remodeling after MI.
- © 2011 by American Heart Association, Inc.