Abstract 12801: Epigallocatechin Gallate Attenuates the Progression of Heart Failure Induced by Heart/muscle-specific Deletion Of Mn-SOD in Mice Through Scavenging Free Radicals and Improving the Cardiac Chronic Inflammation
Background- Heart failure involves a robust inflammatory response, but the involvement of oxidative stress in mediating cardiac remodeling remains incompletely defined.MnSOD is one of the important antioxidant enzyme, catalyzes the conversion of superoxide to hydrogen peroxide, and this deficiency could lead to severe mitochondrial damage. This study examined the beneficial effects of EGCG on the cardiac remodeling and telomere biology in heart/muscle-specific manganese superoxide dismutase-deficient mice (H/M-SOD2−/−), which develop progressive congestive heart failure and exhibit pathology typical of dilated cardiomyopathy.
Methods and Results- H/M-SOD2−/− mice were divided into three groups as follows: receiving normal drinking water (KO), receiving low dose of EGCG (L: 10 mg/L), and receiving high dose of EGCG (H: 100 mg/L) at the age of 8 weeks for 8 weeks. The mice in KO group sustained significantlydilated cardiac remodeling with reduced contractility, which was prevented by the administration of EGCG. Although mortality of KO mice revealed about 50 % at 16 weeks of age, mice receiving EGCG sustained high survival rate. The cardiac dimension in KO mice was notably dilated with reduced cardiac contraction and could be signi[[Unable to Display Character: ﬁ]]cantly prevented by EGCG treatment. The levels of myocardial TBARS (indicating the level of oxidative stress) and free fatty acid were lower in L and H groups as comared with KO group. Increased protein expressions of NOS2, nitrotyrosine, PTX3, BNP, fatty acid synthase and Sirt1 in the heart of KO group were prevented by administration of EGCG. The shortening of telomere length and decreased telomerase activity was observed in the heart of KO mice, which were prevented by EGCG. Protein expression for telomerase reverse transcriptase was downregulated in H/M-SOD2−/− heart tissue as was expression of phospho-Akt and phospho-endothelial nitric oxide synthase (eNOS).
Conclusions- In conclusion, the present study demonstrated that H/M-SOD2−/− mice receiving EGCG sustain lower mortality and exhibit less inflammation and preserved cardiac function and telomere biology. The data suggest that EGCG has the cardioprotective effects against oxidative stress and cardiac dysfunction following left ventricular remodeling.
- © 2012 by American Heart Association, Inc.