Ellagic Acid Prevents Ca2+ Dysregulation and Improves Functional Abnormalities of Ventricular Myocytes via Attenuation of Oxidative Stress in Pathological Cardiac Hypertrophy

The aim of this study was to investigate whether ellagic acid (EA) treatment can prevent changes in contractile function and Ca 2+ regulation of cardiomyocytes in pathologic cardiac hypertrophy. Groups were assigned as Con group; an ISO group in which the rats received isoproterenol alone (5 mg/kg/day); and an ISO + EA group in which the rats received isoproterenol and EA (20 mg/kg/day) for 4 weeks. Subsequently, fractional shortening, intracellular Ca 2+ signals, and L-type Ca 2+ currents of isolated ventricular myocytes were recorded. Protein expression levels were also determined by the Western blotting method. The survival rate was increased, and the upregulated cardiac hypertrophy markers were significantly attenuated with the EA treatment. The fractional shortening and relaxation rate of myocytes was decreased in the ISO group, whereas EA significantly improved these changes. Ventricular myocytes of the ISO + EA rats displayed lower diastolic Ca 2+ levels, higher Ca 2+ transients, shorter Ca 2+ decay, and higher L-type Ca 2+ currents than those of ISO rats. Protein expression analyses indicated that the upregulated p-PLB and p-CaMKII expressions were restored by EA treatment, suggesting improved calcium handling in the ISO + EA rat heart. Moreover, ISO rats displayed significantly increased expression of p-22 phox and p47 phox subunits of NOX2 protein. Expression of the p22 phox subunit was reduced with EA administration, while the decrease in p47 phox did not reach a significant level. The increased ROS impairs Ca 2+ homeostasis and contractile activity of cardiac myocytes, whereas chronic EA administration prevents Ca 2+ dysregulation and functional abnormalities associated with pathological cardiac hypertrophy via the diminution of oxidative stress.