Effects of Methotrexate on Plasma Cytokines and Cardiac Remodeling and Function in Postmyocarditis Rats

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  • Zhengang Zhang
    Department of Cardiovascular Disease, The First People's Hospital of Yangzhou, 45 Taizhou Road, Yangzhou, Jiangsu 225001, China
  • Pei Zhao
    Department of Cardiovascular Disease, The First People's Hospital of Yangzhou, 45 Taizhou Road, Yangzhou, Jiangsu 225001, China
  • Aihua Li
    Department of Cardiovascular Disease, The First People's Hospital of Yangzhou, 45 Taizhou Road, Yangzhou, Jiangsu 225001, China
  • Xiaolei Lv
    Department of Cardiovascular Disease, The First People's Hospital of Yangzhou, 45 Taizhou Road, Yangzhou, Jiangsu 225001, China
  • Yang Gao
    Department of Cardiovascular Disease, The First People's Hospital of Yangzhou, 45 Taizhou Road, Yangzhou, Jiangsu 225001, China
  • Hongguang Sun
    Department of Ultrasonography, The First People's Hospital of Yangzhou, 45 Taizhou Road, Yangzhou, Jiangsu 225001, China
  • Yongling Ding
    Department of Pathology, The First People's Hospital of Yangzhou, 45 Taizhou Road, Yangzhou, Jiangsu 225001, China
  • Jian Liu
    Central Lab, The First People's Hospital of Yangzhou, 45 Taizhou Road, Yangzhou, Jiangsu 225001, China

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<jats:p>Excessive immune activation and inflammatory mediators may play a critical role in the pathogenesis of chronic heart failure. Methotrexate is a commonly used anti-inflammatory and immunosuppressive drug. In this study, we used a rat model of cardiac myosin-induced experimental autoimmune myocarditis to investigate the effects of low-dose methotrexate (0.1 mg/kg/d for 30 d) on the plasma level of cytokines and cardiac remodeling and function. Our study showed that levels of tumor necrosis factor-(TNF-)alpha and interleukin-6 (IL-6) are significantly increased in postmyocarditis rats, compared with the control rats. Methotrexate treatment reduced the plasma levels of TNF-alpha and IL-6 and increased IL-10 level, compared to saline treatment. In addition, postmyocarditis rats showed significant cardiac fibrosis characterized by increased myocardial collagen volume fraction, perivascular collagen area, and the ratio of collagen type I to type III, compared with the control rats. However, MTX treatment not only markedly attenuated cardiac fibrosis, diminished the left ventricular end-diastolic dimension, but also increased the left ventricular ejection fraction and fractional shortening. Collectively, these results suggest that low-dose methotrexate has ability to regulate inflammatory responses and improves cardiac function and hence contributes to prevent the development of postmyocarditis dilated cardiomyopathy.</jats:p>

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