PMID- 16043946
OWN - NLM
STAT- MEDLINE
DCOM- 20051006
LR  - 20191109
IS  - 1349-2365 (Print)
IS  - 1349-2365 (Linking)
VI  - 46
IP  - 3
DP  - 2005 May
TI  - Rapamycin ameliorates experimental autoimmune myocarditis.
PG  - 513-30
AB  - 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.
FAU - Maeda, Kayo
AU  - Maeda K
AD  - Department of Internal Medicine and Cardiology, Kitasato University School of 
      Medicine, Sagamihara, Japan.
FAU - Shioi, Tetsuo
AU  - Shioi T
FAU - Kosugi, Rie
AU  - Kosugi R
FAU - Yoshida, Yuki
AU  - Yoshida Y
FAU - Takahashi, Keiko
AU  - Takahashi K
FAU - Machida, Yoji
AU  - Machida Y
FAU - Izumi, Tohru
AU  - Izumi T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Japan
TA  - Int Heart J
JT  - International heart journal
JID - 101244240
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Interleukin-1)
RN  - 0 (Interleukin-2)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 114471-18-0 (Natriuretic Peptide, Brain)
RN  - 82115-62-6 (Interferon-gamma)
RN  - EC 3.6.4.1 (Myosins)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Animals
MH  - *Autoimmunity
MH  - Cardiomyopathy, Dilated/drug therapy/immunology
MH  - Disease Models, Animal
MH  - Female
MH  - Gene Expression Regulation/*drug effects
MH  - Immunosuppressive Agents/*pharmacology
MH  - Interferon-gamma/blood
MH  - Interleukin-1/blood
MH  - Interleukin-2/blood
MH  - Myocarditis/chemically induced/*drug therapy/*immunology
MH  - Myosins
MH  - Natriuretic Peptide, Brain/blood
MH  - Rats
MH  - Rats, Inbred Lew
MH  - Sirolimus/*pharmacology
MH  - Treatment Outcome
MH  - Tumor Necrosis Factor-alpha/metabolism
EDAT- 2005/07/27 09:00
MHDA- 2005/10/07 09:00
CRDT- 2005/07/27 09:00
PHST- 2005/07/27 09:00 [pubmed]
PHST- 2005/10/07 09:00 [medline]
PHST- 2005/07/27 09:00 [entrez]
AID - JST.JSTAGE/ihj/46.513 [pii]
AID - 10.1536/ihj.46.513 [doi]
PST - ppublish
SO  - Int Heart J. 2005 May;46(3):513-30. doi: 10.1536/ihj.46.513.