| Rapamycin ameliorates experimental autoimmune myocarditis. | |
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MedLine Citation:
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PMID: 16043946 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Myosin-induced autoimmune myocarditis in rats is a model of human dilated cardiomyopathy. Rapamycin is a potent immunosuppressant and specifically inactivates the mammalian target of rapamycin (mTOR). To examine the role of mTOR in autoimmune myocarditis, we administered rapamycin to rats immunized with cardiac myosin. Phosphorylation of p70 ribosomal S6 kinase 1 (S6K1), a target of mTOR, was increased by 6.9 fold in the heart tissue of myosin immunized rats. Rapamycin (2 mg/kg/day) completely suppressed S6K1 and S6 phosphorylation. The amount of interleukin-1beta, interferon-gamma, interleukin-2, or tumor necrosis factor-alpha mRNA in the heart tissue was markedly increased in myosin-immunized rats, and rapamycin significantly attenuated the cytokine gene expressions. Rapamycin improved the survival of the rats and preserved cardiac function. The plasma level of brain natriuretic peptide increased by 4.7 fold in myosin-immunized rats, and rapamycin attenuated the increase in plasma brain natriuretic peptide. The heart weight/tibial length ratio of vehicle-treated myosin-immunized rats was increased by 1.81 +/- 0.06 fold compared with vehicle-treated unimmunized rats, and rapamycin suppressed the increase in heart weight. Rapamycin decreased the cellular infiltration and fibrosis of the myocardium. The amount of phosphorylated S6 was increased in the infiltrating mononuclear cells in vehicle-treated myosin-immunized rats. Rapamycin significantly ameliorated myocardial injury and preserved cardiac function in a rat model of autoimmune myocarditis. |
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Authors:
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Kayo Maeda; Tetsuo Shioi; Rie Kosugi; Yuki Yoshida; Keiko Takahashi; Yoji Machida; Tohru Izumi |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: International heart journal Volume: 46 ISSN: 1349-2365 ISO Abbreviation: - Publication Date: 2005 May |
Date Detail:
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Created Date: 2005-07-26 Completed Date: 2005-10-06 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 101244240 Medline TA: Int Heart J Country: Japan |
Other Details:
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Languages: eng Pagination: 513-30 Citation Subset: IM |
Affiliation:
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Department of Internal Medicine and Cardiology, Kitasato University School of Medicine, Sagamihara, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Autoimmunity* Cardiomyopathy, Dilated / drug therapy, immunology Disease Models, Animal Female Gene Expression Regulation / drug effects* Immunosuppressive Agents / pharmacology* Interferon-gamma / blood Interleukin-1 / blood Interleukin-2 / blood Myocarditis / chemically induced, drug therapy*, immunology* Myosins Natriuretic Peptide, Brain / blood Rats Rats, Inbred Lew Sirolimus / pharmacology* Treatment Outcome Tumor Necrosis Factor-alpha / metabolism |
| Chemical | |
Reg. No./Substance:
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0/Immunosuppressive Agents; 0/Interleukin-1; 0/Interleukin-2; 0/Tumor Necrosis Factor-alpha; 114471-18-0/Natriuretic Peptide, Brain; 53123-88-9/Sirolimus; 82115-62-6/Interferon-gamma; EC 3.6.4.1/Myosins |
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