Epigallocatechin gallate, the major component of polyphenols in green tea, inhibits telomere attrition mediated cardiomyocyte apoptosis in cardiac hypertrophy
Epigallocatechin gallate, the major component of polyphenols in green tea, inhibits telomere attrition mediated cardiomyocyte apoptosis in cardiac hypertrophy
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表没食子儿茶素没食子酸酯是绿茶中多酚的主要成分，可抑制心脏肥大中端粒磨损介导的心肌细胞凋亡。
DOI：
10.1016/j.ijcard.2011.07.083
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发表时间：
2013-01-20
影响因子：
3.5
通讯作者：
Xie, Mei-Lin
中科院分区：
文献类型：
--
作者：
Sheng, Rui;Gu, Zhen-Lun;Xie, Mei-Lin
背景：端粒信号在心功能障碍过程中调控心肌细胞凋亡中起重要作用。在这项研究中，我们研究了绿茶中多酚的主要成分表没食子儿茶素没食子酸酯（EGCG）对压力过载心肌肥厚中端粒依赖性凋亡信号的影响。方法与结果：采用腹主动脉缩窄法建立大鼠心肌肥厚模型。EGCG 50、100mg/kg、槲皮素（Que） 100mg/kg、卡托普利（Cap） 50mg /kg、氯沙坦（Los） 30mg /kg、卡维地洛（Carv） 30mg /kg灌胃6周。主动脉收缩后3、5、7周，心脏重量指数逐渐升高。丙二醛（MDA）含量逐渐升高，超氧化物歧化酶（SOD）活性逐渐降低。进行性心肌细胞凋亡和端粒磨损也被发现。虽然到主动脉收缩后7周，端粒酶逆转录酶（TERT） mRNA未见明显变化，但p53、c-myc的进行性上调，bcl-2、端粒重复结合因子2（TRF2）的下调。EGCG、槲皮素、卡托普利、氯沙坦和卡维地洛均能显著降低肥厚心肌的心重指数和心肌细胞凋亡，但对凋亡相关蛋白bcl-2、p53和c-myc的影响不同。EGCG、槲皮素和卡维地洛具有较强的抗氧化作用，可以降低MDA含量，恢复SOD活性。EGCG、槲皮素和卡维地洛能显著防止端粒磨损和端粒重复结合因子2 （TRF2）丢失，而卡托普利和氯沙坦对氧化应激和端粒信号无影响。结论：压力过载诱导的心肌肥厚引发氧化应激，诱导端粒重复结合因子2丢失，加速端粒缩短。EGCG、槲皮素和卡维地洛具有较强的抗氧化作用，可能通过防止端粒缩短和端粒重复结合因子2 （TRF2）丢失来抑制心肌细胞凋亡。(C) 2011年由爱思唯尔爱尔兰有限公司出版。
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) 50 mg/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(TRF2) 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 (TRF2) 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 (TRF2) loss. (C) 2011 Published by Elsevier Ireland Ltd.