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01-07-2015 | Original Article

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

Authors: Hirofumi Zempo, Yoichiro Sugita, Masahito Ogawa, Ryo Watanabe, Jun-ichi Suzuki, Mitsuaki Isobe

Published in: Heart and Vessels | Issue 4/2015

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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Title: A P2X7 receptor antagonist attenuates experimental autoimmune myocarditis via suppressed myocardial CD4+ T and macrophage infiltration and NADPH oxidase 2/4 expression in mice
Authors: Hirofumi Zempo
Yoichiro Sugita
Masahito Ogawa
Ryo Watanabe
Jun-ichi Suzuki
Mitsuaki Isobe
Publication date: 01-07-2015
Publisher: Springer Japan
Published in: Heart and Vessels / Issue 4/2015
Print ISSN: 0910-8327
Electronic ISSN: 1615-2573
DOI: https://doi.org/10.1007/s00380-014-0527-2

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