Epigallocatechin gallate, the major component of polyphenols in green tea, inhibits telomere attrition mediated cardiomyocyte apoptosis in cardiac hypertrophy.

BACKGROUND: Telomere signaling plays a role in regulating cardiomyocyte apoptosis during cardiac dysfunction. In this study, we investigated the effects of epigallocatechin gallate (EGCG), the major component of polyphenols in green tea, on telomere dependent apoptotic signal in pressure overload cardiac hypertrophy.

METHODS AND RESULTS: Cardiac hypertrophy in rats was established by abdominal aortic constriction (AC). EGCG 50, 100 mg/kg, quercetin (Que) 100mg/kg, captopril (Cap) 50mg/kg, losartan (Los) 30 mg/kg and carvedilol (Carv) 30 mg/kg was intragastrically administered for 6 weeks. Three, five and 7 weeks after aortic constriction, the heart weight indices increased progressively. Malondialdehyde (MDA) contents progressively increased, while superoxide dismutase (SOD) activities decreased. Progressive cardiomyocyte apoptosis and telomere attrition were also found. Although no significant alteration of telomerase reverse transcriptase (TERT) mRNA was found till 7 weeks after aortic constriction, progressive upregulation of p53, c-myc and downregulation of bcl-2, telomere repeat-binding factor 2(TRF(2)) were seen. EGCG, quercetin, captopril, losartan and carvedilol markedly reduced heart weight indices and apoptotic cardiomyocyte in hypertrophic myocardium, but they had different effects on apoptotic related proteins bcl-2, p53 and c-myc. EGCG, quercetin and carvedilol, have potent antioxidant effects as evidenced by reduction of MDA contents and resumption of SOD activities. EGCG, quercetin and carvedilol could prevent telomere attrition and telomere repeat-binding factor 2 (TRF(2)) loss remarkably, whereas captopril and losartan had no effect on oxidative stress and telomere signal.

CONCLUSIONS: Pressure overload induced cardiac hypertrophy initiates oxidative stress, induces telomere repeat-binding factor 2 loss and accelerates telomere shortening in hypertrophic myocardium. EGCG, quercetin and carvedilol with potent antioxidant effect, may inhibit cardiac myocyte apoptosis by preventing telomere shortening and telomere repeat-binding factor 2 (TRF(2)) loss.