Epigallocathechin-3 gallate inhibits cardiac hypertrophy through blocking reactive oxidative species-dependent and -independent signal pathways.
Cardiac hypertrophy is a major cause of morbidity and mortality worldwide. Recent in vitro and in vivo studies have suggested that reactive oxygen species (ROS) may play an important role in cardiac hypertrophy. It was therefore thought to be of particular value to examine the effects of antioxidants on cardiac hypertrophy. Epigallocatechin-3-gallate (EGCG) is a major bioactive polyphenol present in green tea and a potent antioxidant. The current study was designed to test the hypothesis that EGCG inhibits cardiac hypertrophy in vitro and in vivo. In this study, we investigated the effects of EGCG on angiotensin II- (Ang II) and pressure-overload-induced cardiac hypertrophy. Our results showed that EGCG attenuated Ang II- and pressure-overload-mediated cardiac hypertrophy. Both reactive oxygen species generation and NADPH oxidase expressions induced by Ang II and pressure overload were suppressed by EGCG. The increased hypertension by pressure overload was almost completely blocked after EGCG treatment. Further studies showed that EGCG inhibited Ang II-induced NF-kappaB and AP-1 activation. Inhibition of the activity of NF-kappaB was through blocking ROS-dependent p38 and JNK signaling pathways, whereas inhibition of AP-1 activation was via blocking EGFR transactivation and its downstream events ERKs/PI3K/Akt/mTOR/p70(S6K). The combination of these actions resulted in repressing the reactivation of ANP and BNP, and ultimately preventing the progress of cardiac hypertrophy. These findings indicated that EGCG prevents the development of cardiac hypertrophy through ROS-dependent and -independent mechanisms involving inhibition of different intracellular signaling transductional pathways.
Li
Hong-Liang
HL
National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College Beijing, People's Republic of China.
Huang
Yue
Y
Zhang
Chan-Na
CN
Liu
Guang
G
Wei
Yu-Sheng
YS
Wang
Abi-Bing
AB
Liu
Yu-Qing
YQ
Hui
Rui-Tai
RT
Wei
Chiming
C
Williams
G Metville
GM
Liu
De-Pei
DP
Liang
Chih-Chuan
CC
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D000975:Antioxidants / Q000494:pharmacology*; D015152:Blotting, Northern; D015153:Blotting, Western; D006332:Cardiomegaly / Q000209:etiology / Q000517:prevention & control*; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D024202:Electrophoretic Mobility Shift Assay; D004789:Enzyme Activation / Q000187:drug effects; D066246:ErbB Receptors / Q000187:drug effects / Q000378:metabolism; D006973:Hypertension / Q000139:chemically induced / Q000150:complications; D048670:MAP Kinase Kinase 4 / Q000187:drug effects / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D018808:Transcription Factor AP-1 / Q000187:drug effects / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism
D000975:Antioxidants; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D018808:Transcription Factor AP-1; D000804:Angiotensin II; D002392:Catechin; C045651:epigallocatechin gallate; D066246:ErbB Receptors; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4