RGD Reference Report - Prevention of experimental autoimmune myocarditis by hydrodynamics-based naked plasmid DNA encoding CTLA4-Ig gene delivery. - Rat Genome Database

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Prevention of experimental autoimmune myocarditis by hydrodynamics-based naked plasmid DNA encoding CTLA4-Ig gene delivery.

Authors: Abe, S  Hanawa, H  Hayashi, M  Yoshida, T  Komura, S  Watanabe, R  Lie, H  Chang, H  Kato, K  Kodama, M  Maruyama, H  Nakazawa, M  Miyazaki, J  Aizawa, Y 
Citation: Abe S, etal., J Card Fail. 2005 Sep;11(7):557-64.
RGD ID: 7204512
Pubmed: PMID:16198253   (View Abstract at PubMed)
DOI: DOI:10.1016/j.cardfail.2005.04.005   (Journal Full-text)

BACKGROUND: Rat experimental autoimmune myocarditis (EAM) is a T cell-mediated disease that resembled the giant cell myocarditis seen in humans. Soluble CTLA4 improves some autoimmune diseases by blocking costimulatory signals on T cell. We investigated the effect of hydrodynamics-based naked plasmid DNA encoding CTLA4-immunoglobulin (Ig) gene delivery. METHODS AND RESULTS: Lewis rats were immunized with cardiac myosin and treated with hydrodynamic-based transfection, namely a rapid tail vein injection of a large volume of pCAGGS encoding CTLA4-Ig chimera solution on Day 0. The vector-derived CTLA4-Ig mRNA expressions were mainly detected in the liver and plasma CTLA4-Ig protein levels were maintained at about 2 mug/mL during the experiment period. On Day 17, the ratio of heart to body weight, the amount of mRNA of atrial natriuretic peptide, and the inflammatory areas in CTLA4 group were significantly lower than in the control group treated with empty plasmid. Maximum rate of intraventricular pressure rise and decline (dP/dT), minimum dP/dT, left ventricular end-diastolic pressure, and central venous pressure improved significantly after treatment with CTLA4-Ig. On Day 14, expressions of IL-2 in popliteal lymph nodes in the CTLA4-Ig group were significantly lower than in the control group. CONCLUSION: Hydrodynamics-based transfection of plasmid encoding CTLA4-Ig chimera dramatically prevented EAM.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
myocarditis  ISOCtla4 (Rattus norvegicus)7204512; 7204512 RGD 
myocarditis  IMP 7204512 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ctla4  (cytotoxic T-lymphocyte-associated protein 4)

Genes (Mus musculus)
Ctla4  (cytotoxic T-lymphocyte-associated protein 4)

Genes (Homo sapiens)
CTLA4  (cytotoxic T-lymphocyte associated protein 4)


Additional Information