EGCG, a green tea catechin, attenuates the progression of heart failure induced by the heart/muscle-specific deletion of MnSOD in mice

J Cardiol. 2017 Feb;69(2):417-427. doi: 10.1016/j.jjcc.2016.05.019. Epub 2016 Jun 30.

Abstract

Background: Manganese superoxide dismutase (MnSOD) is an important antioxidant enzyme affected in heart/muscle-specific MnSOD-deficient mice (H/M-SOD2-/-), which develop progressive congestive heart failure and exhibit pathology typical of dilated cardiomyopathy.

Methods: In this study we investigated the beneficial effects of epigallocatechin gallate (EGCG) on the cardiac remodeling and telomere biology in H/M-SOD2-/- mice. H/M-SOD2-/- mice were divided into three groups: those receiving normal drinking water (KO), a low dose of EGCG (L: 10mg/L), and a high dose of EGCG (H: 100mg/L) beginning at eight weeks of age and lasting for eight weeks.

Results: The mice in the KO group exhibited significantly dilated cardiac remodeling with reduced contractility, which was prevented by the administration of EGCG. Although the mortality of KO mice was about 50% at 16 weeks of age, the mice that received EGCG had a high survival rate. The cardiac dilatation with reduced cardiac contraction in KO mice was prevented by EGCG treatment. The levels of myocardial oxidative stress and free fatty acids were lower in the group treated with EGCG compared with the KO group. The increased expression of nitric oxide synthase 2, nitrotyrosine, fatty acid synthase, Toll-like receptor 4, and Sirt1 in the KO mice were prevented by EGCG treatment. The shortening of the telomere length, decreased telomerase activity in KO mice were also prevented by EGCG.

Conclusions: H/M-SOD2-/- mice receiving EGCG have a lower mortality rate and exhibit less inflammation and a better preserved cardiac function and telomere biology.

Keywords: Catechin; EGCG; Heart failure; MnSOD; Oxidative stress.

MeSH terms

  • Animals
  • Antioxidants / administration & dosage*
  • Catechin / administration & dosage
  • Catechin / analogs & derivatives*
  • Disease Models, Animal
  • Fatty Acid Synthases / drug effects
  • Fatty Acids, Nonesterified / metabolism
  • Heart Failure / drug therapy*
  • Mice
  • Mice, Knockout
  • Myocardium / metabolism
  • Nitric Oxide Synthase Type II / drug effects
  • Oxidative Stress / drug effects
  • Sirtuin 1 / drug effects
  • Superoxide Dismutase / genetics
  • Telomerase / drug effects
  • Telomere Shortening / drug effects
  • Toll-Like Receptor 4 / drug effects
  • Tyrosine / analogs & derivatives
  • Tyrosine / drug effects
  • Ventricular Remodeling / drug effects

Substances

  • Antioxidants
  • Fatty Acids, Nonesterified
  • Toll-Like Receptor 4
  • 3-nitrotyrosine
  • Tyrosine
  • Catechin
  • epigallocatechin gallate
  • Nitric Oxide Synthase Type II
  • Nos2 protein, rat
  • Superoxide Dismutase
  • Fatty Acid Synthases
  • Telomerase
  • Sirt1 protein, mouse
  • Sirtuin 1