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Effects of HMG-CoA Reductase Inhibitor on Experimental Autoimmune Myocarditis

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Abstract

Purpose

Myocarditis is an acute inflammatory disease of the heart and is often a precursor of dilated cardiomyopathy. Experimental autoimmune myocarditis (EAM) has been used as a model for human myocarditis. The purpose of this study was to investigate the therapeutic role of 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase inhibitor, rosuvastatin, on the development of EAM.

Methods

Experimental autoimmune myocarditis was induced in BALB/c mice by immunization with murine cardiac α-myosin heavy chain (MyHc-α614–629 [Ac-SLKLMATLFSTYASAD-OH]). High-dose (10 mg/kg/day) or low-dose (1 mg/kg/day) rosuvastatin or vehicle was administered orally by gastric gavage to mice with EAM from day 0 to day 21 after immunization. On day 21 after immunization, echocardiography was carried out and the severity of myocarditis was detected by histopathological evaluation. Levels of serum tumor necrosis factor (TNF)-α and interleukin (IL)-6 were measured by ELISA. Histopathology was performed using haematoxylin and eosin. With apoptosis examined by Tunel, the expression of active caspase-3 in myocardium was investigated by immunohistochemistry.

Results

Rosuvastatin attenuated the histopathological severity of myocarditis. Cardiac function was improved in the two rosuvastatin-treated groups compared to the non-treated EAM group (LVFS: high-dose rosuvastatin group [group H], 0.38 ± 0.10%; low-dose rosuvastatin group [group L], 0.34 ± 0.06%; non-treated EAM group [group N], 0.29 ± 0.07%. LVEF: group H, 0.80 ± 0.09%; group L, 0.71 ± 0.07%; group N, 0.68 ± 0.07%). Furthermore, treatment with rosuvastatin decreased the expression levels of TNF-α (group H, 65.19 ± 7.06 pg/ml; group L, 108.20 ± 5.28 pg/ml; group N, 239.34 ± 11.65 pg/ml) and IL-6 (group H, 14.33 ± 2.15 pg/ml; group L, 19.67 ± 3.04 pg/ml; group N, 40.39 ± 7.17 pg/ml). The rates of expression of active Caspase-3 and myocardial apoptosis were positively correlated with the scores for myocardial pathology.

Conclusions

These results demonstrate that administration of rosuvastatin can ameliorate EAM progression, inhibit apoptosis of cardiomyocytes, and preserve cardiac output, and they also suggest rosuvastatin may be a promising novel therapeutic strategy for the clinical treatment of myocarditis.

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Acknowledgements

This work was supported by the National 973 Basic Research Program of China (No.2009CB521904) and the grant of Natural Science Foundation of Shandong Province (Y2007C074). We greatly appreciate Doctor Shanying Huang and Hong Jiang for their excellent technical assistances.

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Authors and Affiliations

  1. The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Shandong University Qilu Hospital, Jinan, Shandong, 250012, China

    Xiaoman Liu, Bo Li, Wenke Wang, Cheng Zhang, Mingxiang Zhang, Yun Zhang, Yanfei Xia, Zhe Dong, Yuan Guo & Fengshuang An

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  1. Xiaoman Liu
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  2. Bo Li
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  3. Wenke Wang
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  4. Cheng Zhang
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Correspondence to Yuan Guo or Fengshuang An.

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Xiaoman Liu and Bo Li contributed equally to this paper.

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Liu, X., Li, B., Wang, W. et al. Effects of HMG-CoA Reductase Inhibitor on Experimental Autoimmune Myocarditis. Cardiovasc Drugs Ther 26, 121–130 (2012). https://doi.org/10.1007/s10557-012-6372-6

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