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A P2X7 receptor antagonist attenuates experimental autoimmune myocarditis via suppressed myocardial CD4+ T and macrophage infiltration and NADPH oxidase 2/4 expression in mice

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Abstract

Myocarditis is a clinically serious disease; however, no effective treatment has been elucidated. The P2X7 receptor is related to the pathophysiology of inflammation in many cardiovascular diseases. The P2X7 receptor antagonist is promising as an immunosuppressive treatment; however, its role in myocarditis is still to be established. To clarify the role of the P2X7 receptor, we used a murine experimental autoimmune myocarditis (EAM) model. Mice were immunized on day 0 and 7 with synthetic cardiac myosin peptide to establish EAM. The mice with induced EAM were treated with A740003, the P2X7 receptor antagonist (n = 10), or not treated (n = 11); hearts were harvested on day 21. The P2X7 receptor antagonist improved myocardial contraction of the EAM hearts via suppressed infiltration of CD4+ T cells and macrophages. Similarly, mRNA expression of interleukin 1 beta, the P2X7 receptor and NADPH oxidase 2/4 was lower in the heart of the P2X7 receptor antagonist-treated group compared to the non-treat group. The P2X7 receptor antagonist suppressed EAM development; thus, this inhibition is promising for treating clinical myocarditis.

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Acknowledgments

We would like to thank Ms. Noriko Tamura and Ms. Yasuko Matsuda for their excellent technical assistance. This study was supported by Takeda Science Foundation, Suzuken Memorial Foundation, the grant from the Research Foundation for Pharmaceutical Sciences, and the Japan Society for the Promotion of Science (JSPS) through its “Funding Program for World-Leading Innovative R&D on Science and Technology (FIRST Program).”

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The authors have no financial conflict of interest.

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Authors and Affiliations

  1. Department of Cardiovascular Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan

    Hirofumi Zempo, Yoichiro Sugita, Masahito Ogawa, Ryo Watanabe & Mitsuaki Isobe

  2. Department of Advanced Clinical Science and Therapeutics, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan

    Jun-ichi Suzuki

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  1. Hirofumi Zempo
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  2. Yoichiro Sugita
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Correspondence to Jun-ichi Suzuki.

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Zempo, H., Sugita, Y., Ogawa, M. et al. A P2X7 receptor antagonist attenuates experimental autoimmune myocarditis via suppressed myocardial CD4+ T and macrophage infiltration and NADPH oxidase 2/4 expression in mice. Heart Vessels 30, 527–533 (2015). https://doi.org/10.1007/s00380-014-0527-2

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  • DOI: https://doi.org/10.1007/s00380-014-0527-2

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