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European Journal of Heart Failure Advance Access originally published online on February 12, 2009
European Journal of Heart Failure 2009 11(4):349-353; doi:10.1093/eurjhf/hfp023
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Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2009. For permissions please email: journals.permissions@oxfordjournals.org.

Anti-inflammatory effects of eplerenone on viral myocarditis

Jie Xiao1,3, Miho Shimada1, Wenling Liu1,2, Dayi Hu2 and Akira Matsumori1,*

1 Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, 54 Kawahara-cho Shogoin, Sakyo-ku, Kyoto 606-8507, Japan
2 Peking University People’s Hospital, People’s Republic of China
3 Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China

* Corresponding author. Tel: +81 75 751 3186, Fax: +81 75 751 6477, Email: amat{at}kuhp.kyoto-u.ac.jp


  Abstract

Aims: Inflammation contributes to increased cardiovascular morbidity and mortality associated with activation of the renin–angiotensin–aldosterone system. The aim of this study was to investigate whether eplerenone, a selective aldosterone receptor antagonist, has anti-inflammatory effects on viral myocarditis.

Methods and results: Four-week-old inbred male DBA/2 mice were inoculated intraperitoneally with 10 plaque-forming units (pfu) of the encephalomyocarditis (EMC) virus. Mice were fed with standard chow (control) or with chow containing 2.5 mg/kg of eplerenone, starting either on day 0 (inoculation) or day 7. Survival at 28 days was significantly higher in the mice which started eplerenone treatment on day 0 (35 vs. 15% in controls, each n = 40, P < 0.05). The area of myocardial fibrosis on day 28 was significantly smaller in the eplerenone-treated mice than in controls (19.8 ± 2.6%, n = 14, vs. 33.4 ± 5.4%, n = 6, mean ± SEM, P < 0.05). Gene expression of mouse mast cell proteases-4 and -5, matrix metalloproteinase-9, and type I procollagen on day 6 after EMC virus inoculation was significantly decreased in the hearts of eplerenone-treated mice.

Conclusion: These results suggest that eplerenone has anti-inflammatory effects, and exerts its beneficial effects on viral myocarditis by suppression of genes related to mast cells and cardiac remodelling in the hearts of mice.

Key Words: Viruses • Myocarditis • Inflammation • Mast cells • Eplerenone • Fibrosis • Heart failure

Received October 30, 2008; Revised December 12, 2008; Accepted December 17, 2008


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