© 2003 by European Society of Cardiology
Copyright © 2003, European Society of Cardiology
Peroxisome proliferation-activated receptor-
ligands ameliorate experimental autoimmune myocarditis
aDepartment of Cardiovascular Medicine, First Hospital of Xi’an Jiaotong University, No. 1 Jiankang Road, Xi’an, Shaanxi 710061, China
bDepartment of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan
zuyiyuan{at}mail.xjtu.edu.cn
* Corresponding author. Tel.: +86-29-532-4021; fax: +86-29-526-3190.
Background: Peroxisome proliferator-activated receptor-
(PPAR-) ligands have been shown to ameliorate a variety of inflammatory conditions. The present study tested the hypothesis that PPAR- ligands reduce experimental autoimmune myocarditis (EAM) associated with inhibition of the expansion and activation of T cells, as well as suppression of the expression of proinflammatory cytokines. Methods and results: EAM was induced in Lewis rats by immunization with porcine cardiac myosin. PPAR- ligands, 15-deoxy-
12,14-PGJ2 (15d-PGJ2) 200 µg/kg/day i.p. and pioglitazone (PIO) 10 mg/kg/day orally, were administered for 3 weeks to rats with EAM. The results showed that enhanced PPAR- expression was prominently stained in the nuclear and perinuclear regions of infiltrating inflammatory cells. Administration of PPAR- ligands markedly reduced the severity of myocarditis, as shown by comparing the heart weight/body weight ratio, pericardial effusion scores, macroscopic scores and microscopic scores. PPAR- ligands suppressed myocardial mRNA expression of inflammatory cytokines and the expression of interleukin (IL)-1β protein in rats with EAM. In addition, 15d-PGJ2 and PIO treatment suppressed the proliferative response and interferon- production of T cell-enriched splenocytes from rats with EAM. Furthermore, the cytotoxic activity and myocardiogenic potential of these T cells were inhibited by 15d-PGJ2 treatment. Conclusions: PPAR- may play a role in the pathophysiology of EAM. PPAR- ligands ameliorate the EAM associated with suppression of the expansion and activation of myocardiogenic T cells, as well as inhibition of the expression of proinflammatory cytokines. These results suggest that PPAR- ligands such as 15d-PGJ2 and PIO may have the potential to modulate human inflammatory heart diseases such as myocarditis.
KEYWORDS Myocarditis; Immunity; T cells; PPAR-; Cytokines
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