Autoimmunity against M 2 muscarinic acetylcholine receptor induces myocarditis and leads to a dilated cardiomyopathy-like phenotype

Akihiro Yoshizawa, Shigenori Nagai, Yukiko Baba, Taketo Yamada, Minoru Matsui, Hikaru Tanaka, Shun ichiro Miyoshi, Masayuki Amagai, Tsutomu Yoshikawa, Keiichi Fukuda, Satoshi Ogawa, Shigeo Koyasu

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Patients with dilated cardiomyopathy (DCM) often have autoantibodies against cardiac antigens including the M 2 muscarinic acetylcholine receptor (M 2R). To elucidate the role of autoimmunity against M 2R in disease development, we induced an immune response against M 2R by adoptive transfer into Rag2 -/- mice of splenocytes from M 2R -/- mice immunized with a recombinant M 2R protein. T lymphocytes transiently infiltrated the heart in recipient mice followed by morphological changes in cardiomyocytes. These mice produced IgG antibodies against M 2R, which bound to cardiomyocytes in vivo and decreased the amplitude of calcium signals in isolated rat cardiomyocytes in vitro. Recipient mice showed increased heart weights associated with increased intraventricular diameter, decreased systolic function, and increased action potential duration, which are characteristics of DCM. Our results suggest that myocarditis and DCM associated with the presence of anti-M 2R antibodies are autoimmune diseases with a risk of progressing to the terminal stage. Our mouse model will be useful in the analysis of the molecular mechanisms of disease progression and the development of new therapies for DCM.

Original languageEnglish
Pages (from-to)1152-1163
Number of pages12
JournalEuropean Journal of Immunology
Volume42
Issue number5
DOIs
Publication statusPublished - 2012 May

Keywords

  • Autoimmune myocarditis
  • Dilated cardiomyopathy
  • M muscarinic acetylcholine receptor

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Yoshizawa, A., Nagai, S., Baba, Y., Yamada, T., Matsui, M., Tanaka, H., Miyoshi, S. I., Amagai, M., Yoshikawa, T., Fukuda, K., Ogawa, S., & Koyasu, S. (2012). Autoimmunity against M 2 muscarinic acetylcholine receptor induces myocarditis and leads to a dilated cardiomyopathy-like phenotype. European Journal of Immunology, 42(5), 1152-1163. https://doi.org/10.1002/eji.201142104