Background Myosin-induced autoimmune myocarditis of rats is a model of human dilated cardiomyopathy. Resveratrol is a natural polyphenol found in grapes and wine that is reported to have cardioprotective and immunomodulatory effects. Methods and Results To examine the effect of resveratrol on myocarditis, vehicle or resveratrol (50mg/kg per day) was administered to cardiac myosin immunized rats I day before the immunization. At 14 days after immunization, resveratrol had preserved cardiac function of myosin-immunized rats according to echocardiographic analysis. The heart weight/tibial length ratio of vehicle-treated myosin-immunized rats was increased by 1.8-fold compared with unimmunized rats, and resveratrol attenuated the heart weight increase. Resveratrol significantly decreased cellular infiltration, fibrosis, and expression of inflammatory cytokines in the myocardium. Expressions of antioxidant genes were increased in myosin-immunized hearts, and resveratrol decreased those expressions. Resveratrol also attenuated myocarditis 21 days after immunization. SIRT1, a potential effector of resveratrol, was increased in the myocardium of myosin-immunized rats compared with unimmunized rats. The SIRT1 protein was localized mainly in infiltrating mononuclear cells. Conclusions Resveratrol significantly ameliorated myocardial injury and preserved cardiac function in a rat model of autoimmune myocarditis. Resveratrol may be a therapeutic modality for myocarditis.
机构:
Tokyo Med & Dent Univ, Dept Cardiovasc Med, Tokyo, JapanTokyo Med & Dent Univ, Dept Cardiovasc Med, Tokyo, Japan
Shiheido-Watanabe, Yuka
Maejima, Yasuhiro
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Tokyo Med & Dent Univ, Dept Cardiovasc Med, Tokyo, JapanTokyo Med & Dent Univ, Dept Cardiovasc Med, Tokyo, Japan
Maejima, Yasuhiro
Kasama, Takeshi
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Tokyo Med & Dent Univ, Res Ctr Med & Dent Sci, Tokyo, JapanTokyo Med & Dent Univ, Dept Cardiovasc Med, Tokyo, Japan
Kasama, Takeshi
Tamura, Natsuko
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Tokyo Med & Dent Univ, Dept Cardiovasc Med, Tokyo, JapanTokyo Med & Dent Univ, Dept Cardiovasc Med, Tokyo, Japan
Tamura, Natsuko
Nakagama, Shun
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Tokyo Med & Dent Univ, Dept Cardiovasc Med, Tokyo, JapanTokyo Med & Dent Univ, Dept Cardiovasc Med, Tokyo, Japan
Nakagama, Shun
Ito, Yusuke
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Tokyo Med & Dent Univ, Dept Cardiovasc Med, Tokyo, JapanTokyo Med & Dent Univ, Dept Cardiovasc Med, Tokyo, Japan
Ito, Yusuke
Hirao, Kenzo
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Tokyo Med & Dent Univ, Dept Cardiovasc Med, Tokyo, Japan
AOI Universal Hosp, Dept Cardiovasc Med, Kawasaki, Kanagawa, JapanTokyo Med & Dent Univ, Dept Cardiovasc Med, Tokyo, Japan
Hirao, Kenzo
Isobe, Mitsuaki
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Tokyo Med & Dent Univ, Dept Cardiovasc Med, Tokyo, Japan
Japan Res Promot Soc Cardiovasc Dis, Sakakibara Heart Inst, Tokyo, JapanTokyo Med & Dent Univ, Dept Cardiovasc Med, Tokyo, Japan
Isobe, Mitsuaki
Sasano, Tetsuo
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Tokyo Med & Dent Univ, Dept Cardiovasc Med, Tokyo, JapanTokyo Med & Dent Univ, Dept Cardiovasc Med, Tokyo, Japan
机构:
Toho Univ, Dept Internal Med, Div Neurol, Grad Sch Med, Tokyo, Japan
Toho Univ, Dept Neurol, Ohashi Med Ctr, 2-22-36 Ohashi,Meguro Ku, Tokyo 1538515, JapanToho Univ, Dept Internal Med, Div Neurol, Grad Sch Med, Tokyo, Japan
Uchi, Takafumi
Konno, Shingo
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Toho Univ, Dept Internal Med, Div Neurol, Grad Sch Med, Tokyo, Japan
Toho Univ, Dept Neurol, Ohashi Med Ctr, 2-22-36 Ohashi,Meguro Ku, Tokyo 1538515, JapanToho Univ, Dept Internal Med, Div Neurol, Grad Sch Med, Tokyo, Japan
Konno, Shingo
Kihara, Hideo
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Toho Univ, Dept Internal Med, Div Neurol, Grad Sch Med, Tokyo, Japan
Toho Univ, Dept Neurol, Ohashi Med Ctr, 2-22-36 Ohashi,Meguro Ku, Tokyo 1538515, JapanToho Univ, Dept Internal Med, Div Neurol, Grad Sch Med, Tokyo, Japan
Kihara, Hideo
Fujioka, Toshiki
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Toho Univ, Dept Internal Med, Div Neurol, Grad Sch Med, Tokyo, Japan
Toho Univ, Dept Neurol, Ohashi Med Ctr, 2-22-36 Ohashi,Meguro Ku, Tokyo 1538515, JapanToho Univ, Dept Internal Med, Div Neurol, Grad Sch Med, Tokyo, Japan