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Peroxisome proliferation-activated receptor-gamma ligands ameliorate experimental autoimmune myocarditis.
Cardiovasc Res. 2003 Sep 01; 59(3):685-94.CR

Abstract

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.

Authors+Show Affiliations

Department of Cardiovascular Medicine, First Hospital of Xi'an Jiaotong University, No. 1 Jiankang Road, Xi'an, Shaanxi 710061, China. zuyiyuan@mail.xjtu.edu.cnNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

14499870

Citation

Yuan, Zuyi, et al. "Peroxisome Proliferation-activated Receptor-gamma Ligands Ameliorate Experimental Autoimmune Myocarditis." Cardiovascular Research, vol. 59, no. 3, 2003, pp. 685-94.
Yuan Z, Liu Y, Liu Y, et al. Peroxisome proliferation-activated receptor-gamma ligands ameliorate experimental autoimmune myocarditis. Cardiovasc Res. 2003;59(3):685-94.
Yuan, Z., Liu, Y., Liu, Y., Zhang, J., Kishimoto, C., Wang, Y., Ma, A., & Liu, Z. (2003). Peroxisome proliferation-activated receptor-gamma ligands ameliorate experimental autoimmune myocarditis. Cardiovascular Research, 59(3), 685-94.
Yuan Z, et al. Peroxisome Proliferation-activated Receptor-gamma Ligands Ameliorate Experimental Autoimmune Myocarditis. Cardiovasc Res. 2003 Sep 1;59(3):685-94. PubMed PMID: 14499870.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Peroxisome proliferation-activated receptor-gamma ligands ameliorate experimental autoimmune myocarditis. AU - Yuan,Zuyi, AU - Liu,Yan, AU - Liu,Yu, AU - Zhang,Jijun, AU - Kishimoto,Chiharu, AU - Wang,Yanni, AU - Ma,Aiqun, AU - Liu,Zhiquan, PY - 2003/9/23/pubmed PY - 2004/1/15/medline PY - 2003/9/23/entrez SP - 685 EP - 94 JF - Cardiovascular research JO - Cardiovasc Res VL - 59 IS - 3 N2 - 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. SN - 0008-6363 UR - https://www.unboundmedicine.com/medline/citation/14499870/Peroxisome_proliferation_activated_receptor_gamma_ligands_ameliorate_experimental_autoimmune_myocarditis_ L2 - https://academic.oup.com/cardiovascres/article-lookup/doi/10.1016/s0008-6363(03)00457-7 DB - PRIME DP - Unbound Medicine ER -