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.
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.
authors.affiliation: Department of Cardiovascular Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Zempo
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Sugita
authors.forename: Masahito
authors.initials: M
authors.lastname: Ogawa
authors.forename: Ryo
authors.initials: R
authors.lastname: Watanabe
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Suzuki
authors.forename: Mitsuaki
authors.initials: M
authors.lastname: Isobe
mesh_terms: D000081:Acetamides / Q000627:therapeutic use*; D000818:Animals; D001327:Autoimmune Diseases / Q000188:drug therapy*; D004195:Disease Models, Animal; D007249:Inflammation / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009205:Myocarditis / Q000188:drug therapy*; D009206:Myocardium / Q000473:pathology; D019255:NADPH Oxidases / Q000378:metabolism*; D058920:Purinergic P2X Receptor Antagonists / Q000627:therapeutic use*; D011804:Quinolines / Q000627:therapeutic use*; D058486:Receptors, Purinergic P2X7 / Q000378:metabolism
chemical_list: C515928:(N-(1-(((cyanoimino)(5-quinolinylamino) methyl) amino)-2,2-dimethylpropyl)-2-(3,4-dimethoxyphenyl)acetamide); D000081:Acetamides; D058920:Purinergic P2X Receptor Antagonists; D011804:Quinolines; D058486:Receptors, Purinergic P2X7; D019255:NADPH Oxidases