Document Detail


Rapamycin ameliorates experimental autoimmune myocarditis.
MedLine Citation:
PMID:  16043946     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Kayo Maeda; Tetsuo Shioi; Rie Kosugi; Yuki Yoshida; Keiko Takahashi; Yoji Machida; Tohru Izumi
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  International heart journal     Volume:  46     ISSN:  1349-2365     ISO Abbreviation:  -     Publication Date:  2005 May 
Date Detail:
Created Date:  2005-07-26     Completed Date:  2005-10-06     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  101244240     Medline TA:  Int Heart J     Country:  Japan    
Other Details:
Languages:  eng     Pagination:  513-30     Citation Subset:  IM    
Affiliation:
Department of Internal Medicine and Cardiology, Kitasato University School of Medicine, Sagamihara, Japan.
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MeSH Terms
Descriptor/Qualifier:
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:
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

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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