Peroxisome proliferation-activated receptor-gamma ligands ameliorate experimental autoimmune myocarditis.


BACKGROUND:Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) ligands have been shown to ameliorate a variety of inflammatory conditions. The present study tested the hypothesis that PPAR-gamma 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-gamma ligands, 15-deoxy-Delta(12,14)-PGJ(2) (15d-PGJ(2)) 200 microg/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-gamma expression was prominently stained in the nuclear and perinuclear regions of infiltrating inflammatory cells. Administration of PPAR-gamma 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-gamma ligands suppressed myocardial mRNA expression of inflammatory cytokines and the expression of interleukin (IL)-1beta protein in rats with EAM. In addition, 15d-PGJ(2) and PIO treatment suppressed the proliferative response and interferon-gamma 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-PGJ(2) treatment. CONCLUSIONS:PPAR-gamma may play a role in the pathophysiology of EAM. PPAR-gamma 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-gamma ligands such as 15d-PGJ(2) and PIO may have the potential to modulate human inflammatory heart diseases such as myocarditis.


Cardiovasc Res


Cardiovascular research


Yuan Z,Liu Y,Liu Y,Zhang J,Kishimoto C,Wang Y,Ma A,Liu Z




Has Abstract


2003-09-01 00:00:00














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    pub_type: 杂志文章


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    更新日期:2014-04-01 00:00:00

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    pub_type: 杂志文章


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    pub_type: 杂志文章


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    pub_type: 杂志文章


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    journal_title:Cardiovascular research

    pub_type: 杂志文章


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    pub_type: 杂志文章


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    pub_type: 杂志文章


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    pub_type: 杂志文章


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    更新日期:1991-07-01 00:00:00

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    pub_type: 杂志文章,评审


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    pub_type: 杂志文章,评审


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    更新日期:2012-05-01 00:00:00

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    更新日期:2008-08-01 00:00:00

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    更新日期:2010-04-01 00:00:00

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    pub_type: 杂志文章


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    pub_type: 杂志文章


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    pub_type: 杂志文章


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    更新日期:2010-08-01 00:00:00

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    journal_title:Cardiovascular research

    pub_type: 杂志文章


    authors: Li HY,Liu XL,Liu YT,Jia ZK,Filep JG,Potempa LA,Ji SR,Wu Y

    更新日期:2019-02-01 00:00:00

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    pub_type: 杂志文章


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    journal_title:Cardiovascular research

    pub_type: 杂志文章


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    pub_type: 杂志文章


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    journal_title:Cardiovascular research

    pub_type: 杂志文章


    authors: Bevan L,Lim ZW,Venkatesh B,Riley PR,Martin P,Richardson RJ

    更新日期:2020-06-01 00:00:00