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Immunomodulation by atorvastatin upregulates expression of gap junction proteins in coxsackievirus B3 (CVB3)-induced myocarditis

Inflammation Research volume 59, pages 255–262 (2010)Cite this article

Abstract

Objective

To investigate the effect of atorvastatin on myocardial expression of gap junction proteins, connexins (Cxs), during coxsackievirus B3 (CVB3)-induced myocarditis.

Methods

Viral myocarditis was induced in mice by inoculation with CVB3. Atorvastatin (5 or 10 mg kg−1 day−1) or saline was administered by daily oral gavage from the day of induction of viral myocarditis to the day of sacrifice. Fourteen days after injection of CVB3, animals were sacrificed. Alterations in myocardial Cxs expression were examined by RT-PCR, immunoblot, and immunohistochemistry. Plasma levels of TNF-α and IFN-γ were measured by ELISA.

Results

Fourteen days after inoculation with CVB3, myocardial expression of Cx43 and Cx45 was significantly downregulated. Treatment with atorvastatin not only reduced the overproduction of TNF-α and IFN-γ, but also enhanced the expression of Cx43 and Cx45, therefore attenuating myocardial injury and improving the survival rate of viral myocarditis.

Conclusion

This study shows for the first time that myocardial expression of Cxs is downregulated during CVB3-induced myocarditis and that immunomodulation by atorvastatin could restore the impaired gap junction channels and improve the outcome of viral myocarditis.

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Acknowledgments

This work was supported by the Science and Technology Commission of Shanghai Municipality (grant no. 024119058).

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Affiliations

  1. Department of Cardiology, Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, 639 Zhizaoju Road, 200011, Shanghai, China

    Alian Zhang, Huili Zhang & Shiyao Wu

Authors
  1. Alian Zhang
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  2. Huili Zhang
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  3. Shiyao Wu
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Corresponding author

Correspondence to Shiyao Wu.

Additional information

A. Zhang and H. Zhang contributed equally to the work.

Responsible Editor: M. Katori.

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Zhang, A., Zhang, H. & Wu, S. Immunomodulation by atorvastatin upregulates expression of gap junction proteins in coxsackievirus B3 (CVB3)-induced myocarditis. Inflamm. Res. 59, 255–262 (2010). https://doi.org/10.1007/s00011-009-0093-8

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  • DOI: https://doi.org/10.1007/s00011-009-0093-8

Keywords

  • Viral myocarditis
  • Connexin
  • Inflammation
  • Atorvastatin