Int J Cardiol 2011 Oct; [IF:6.802]
Epigallocatechin gallate, the major component of polyphenols in green tea, inhibits telomere attrition mediated cardiomyocyte apoptosis in cardiac hypertrophy.
Sheng R , Gu ZL , Xie ML .
Suzhou Institute of Chinese Meteria Medica, Department of Pharmacology, Medical School of Suzhou University, 215123 Suzhou, China; Laboratory of Aging and Nervous Diseases, Department of Pharmacology, Medical School of Suzhou University, 215123 Suzhou, China.
苏州大学医学院药理学教研室，衰老与神经疾病实验室，中国科学院苏州纳米技术与纳米仿生研究所
Abstract
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, 100mg/kg, quercetin (Que) 100mg/kg, captopril (Cap) 50mg/kg, losartan (Los) 30mg/kg and carvedilol (Carv) 30mg/kg was intragastrically administered for 6weeks. Three, five and 7weeks 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 7weeks 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.
摘要
背景：
端粒能在心脏功能发生障碍时起到调节心肌细胞凋亡的功能。在本研究中，我们调查了绿茶中多酚类的主要成分茶多酚（EGCG）对在压力过载的心肌肥厚中端粒影响的凋亡信号的作用。
结果和讨论：
老鼠的心脏肥大是通过腹主动脉缩窄（AC）建立的。茶多酚50（EGCG 50），100毫克/千克，槲皮素(Que)100毫克/公斤，卡托普利（Cap）50毫克/公斤，氯沙坦（Los），30毫克/公斤，卡维地洛(Carv)30毫克/公斤灌胃给药6周。
主动脉缩窄后的第3,5,7周，心脏重量出现逐步增加，丙二醛（MDA）含量逐渐增加，而而超氧化物歧化酶(SOD)活性降低。同时也发现了心肌细胞凋亡和端粒磨损。尽管主动脉缩窄7周之后没有发现端粒逆转录基因变更，但是出现了P53，c-myc增加，bcl-2和端粒重复序列结合因子2（TRF（2））降低。茶多酚，槲皮素，卡托普利，氯沙坦，卡维地洛能明显降低心脏重量和在心脏肥大中的心肌凋亡，但是他们能不同程度的影响与凋亡有关的蛋白bcl-2，p53和c-myc。EGCG、槲皮苷和卡维地洛能有很强的抗氧化效果，明显降低MDA的含量和SOD的恢复活动。EGCG、槲皮苷和卡维地洛能防止端粒磨损和端粒重复序列结合因子2（TRF（2））损失，而卡托普利和氯沙坦不会影响氧化应激和端粒信号。
结论：
压力诱导心脏肥大能导致氧化应激，包括端粒重复序列结合因子2损失和加速心肌肥大中的端粒缩短。EGCG、槲皮苷和卡维地洛具有很好的抗氧化作用，可以通过防止端粒缩短和端粒重复序列结合因子2损失来抑制心肌细胞凋亡。
