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


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.


CONCLUSIONS
Hydrodynamics-based transfection of plasmid encoding CTLA4-Ig chimera dramatically prevented EAM.
Abe
Satoru
S
Division of Cardiology, Niigata University Graduate School of Medical and Dental Science, Osaka, Japan.
Hanawa
Haruo
H
Hayashi
Manabu
M
Yoshida
Tsuyoshi
T
Komura
Satoru
S
Watanabe
Ritsuo
R
Lie
Hui
H
Chang
He
H
Kato
Kiminori
K
Kodama
Makoto
M
Maruyama
Hiroki
H
Nakazawa
Mikio
M
Miyazaki
Junichi
J
Aizawa
Yoshifusa
Y
D000069594:Abatacept; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism; D001327:Autoimmune Diseases / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D004195:Disease Models, Animal; D015316:Genetic Therapy / Q000379:methods*; D018796:Immunoconjugates / Q000235:genetics* / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D008198:Lymph Nodes / Q000378:metabolism; D008297:Male; D009205:Myocarditis / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D010957:Plasmids / Q000235:genetics; D011150:Popliteal Artery / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D013997:Time Factors; D014162:Transfection / Q000379:methods; D017725:Ventricular Pressure / Q000502:physiology
D018796:Immunoconjugates; D007376:Interleukin-2; D012333:RNA, Messenger; D000069594:Abatacept; D009320:Atrial Natriuretic Factor