Abstract 16294: Chronic Alcohol Feeding Increases miR-214 and Down regulates Bcl-2 in Heart with Asymptomatic Cardiac Dysfunction
Background: Abusive chronic alcohol consumption over a long period can cause metabolic changes in heart and is a risk factor for non-ischemic cardiomyopathy. Alcohol abusers have no clinical manifestation and remain asymptomatic until challenged with stress, such as cardiac ischemia. Recent study shows MicroRNA-214 (miR-214) as an excellent sensor of underlying stress signals that leads to harmful effects. Therefore we designed this chronic study in mice to diagnose the changes in miR-214 level and its targets and use sildenafil, a cardio protective drug to prevent the heart from alcohol induced injury.
Methods and Results: Adult male 12-14 weeks old FVB mice were grouped to receive unlimited access to normal liquid diet as control (n =6) or Alcohol diet (35 % of daily energy intake, n=7) or alcohol with sildenafil (1mg/kg ;n=6) for 14 weeks. Animal groups fed with alcohol or sildenafil with alcohol diet showed increased volume consumption and a loss in body weight (Fig.1&2). Echocardiography showed no significant difference in the Ejection Fraction (EF) between control, alcohol and alcohol with sildenafil groups (Fig.3). Real time PCR analysis using TaqMan microRNA probe showed 2.6 fold increase in miR-214 with alcohol feeding (Fig 4). Protein analysis showed downregulation of Bcl-2, a target of mir-214 and an increase in ERK-1/2 Phosphorylation, a stress marker with alcohol treatment (Fig.5). Sildenafil blocked the upregulation of mir-214 and increased the level of Bcl-2 and also alleviated the stress by reducing ERK-1/2 Phosphorylation.
Conclusion: The finding demonstrates new mechanism in alcohol cardiomyopathy in which miR-214 repressed Bcl-2 protein and sildenafil effectively decreased the level of miR-214 and elevated the level of Bcl-2, an antiapoptotic protein. Sildenafil also alleviated the stress on heart by reducing ERK-1/2 phosphorylation. Early stage intervention in ACM can prevent the adverse effect of alcohol injury to heart.
Author Disclosures: A. Samidurai: None. L. Xi: None. A. Das: None. F.N. Salloum: None. R.C. Kukreja: None.
- © 2014 by American Heart Association, Inc.