Biological actions of green tea catechins on cardiac troponin C.
OBJECTIVE
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.


METHODS
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.


RESULTS
(-)-Epicatechin-3-gallate (ECg) and (-)-epigallocatechin-3-gallate (EGCg), but not their stereoismers (-)-catechin-3-gallate and (-)-gallocatechin-3-gallate, decreased cardiac myofilament Ca(2+) 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 Ca(2+) sensitivity in a mouse model of hypertrophic cardiomyopathy.


CONCLUSIONS
The green tea catechins, ECg and EGCg, are Ca(2+) 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 Ca(2+) sensitivity of cardiac myofilaments.
Department of Clinical Pharmacology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Naoto
N
Tadano
Cheng-Kun
CK
Du
Fumiaki
F
Yumoto
Sachio
S
Morimoto
Mika
M
Ohta
Ming-Fang
MF
Xie
Koji
K
Nagata
Dong-Yun
DY
Zhan
Qun-Wei
QW
Lu
Yoshikazu
Y
Miwa
Fumi
F
Takahashi-Yanaga
Masaru
M
Tanokura
Iwao
I
Ohtsuki
Toshiyuki
T
Sasaguri
D008841:Actin Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002312:Cardiomyopathy, Hypertrophic / Q000188:drug therapy* / Q000503:physiopathology; D002392:Catechin / Q000031:analogs & derivatives / Q000302:isolation & purification / Q000494:pharmacology*; D004195:Disease Models, Animal; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009200:Myocardial Contraction / Q000187:drug effects; D058525:Quartz Crystal Microbalance Techniques; D011817:Rabbits; D013237:Stereoisomerism; D013662:Tea / Q000737:chemistry*; D019209:Troponin C / Q000187:drug effects* / Q000378:metabolism
D013662:Tea; D019209:Troponin C; D002392:Catechin; D002118:Calcium