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Biological actions of green tea catechins on cardiac troponin C
Authors:Tadano Naoto  Du Cheng-Kun  Yumoto Fumiaki  Morimoto Sachio  Ohta Mika  Xie Ming-Fang  Nagata Koji  Zhan Dong-Yun  Lu Qun-Wei  Miwa Yoshikazu  Takahashi-Yanaga Fumi  Tanokura Masaru  Ohtsuki Iwao  Sasaguri Toshiyuki
Affiliation:Department of Clinical Pharmacology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Abstract:

BACKGROUND AND PURPOSE

Catechins, biologically active polyphenols in green tea, are known to have a protective effect against cardiovascular diseases. In this study, we investigated direct actions of green tea catechins on cardiac muscle function to explore their uses as potential drugs for cardiac muscle disease.

EXPERIMENTAL APPROACH

The effects of catechins were systematically investigated on the force-pCa relationship in skinned cardiac muscle fibres to determine their direct effects on cardiac myofilament contractility. The mechanisms of action of effective catechins were investigated using troponin exchange techniques, quartz crystal microbalance, nuclear magnetic resonance and a transgenic mouse model.

KEY RESULTS

(-)-Epicatechin-3-gallate (ECg) and (-)-epigallocatechin-3-gallate (EGCg), but not their stereoismers (-)-catechin-3-gallate and (-)-gallocatechin-3-gallate, decreased cardiac myofilament Ca2+ sensitivity probably through its interaction with cardiac troponin C. EGCg restored cardiac output in isolated working hearts by improving diastolic dysfunction caused by increased myofilament Ca2+ sensitivity in a mouse model of hypertrophic cardiomyopathy.

CONCLUSIONS AND IMPLICATIONS

The green tea catechins, ECg and EGCg, are Ca2+ desensitizers acting through binding to cardiac troponin C. These compounds might be useful compounds for the development of therapeutic agents to treat the hypertrophic cardiomyopathy caused by increased Ca2+ sensitivity of cardiac myofilaments.
Keywords:catechin   gallate   troponin   calcium sensitivity   cardiomyopathy
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