Leukotriene B4 receptor 1 exacerbates inflammation following myocardial infarction

Yuma Horii, Michio Nakaya, Hiroki Ohara, Hiroaki Nishihara, Kenji Watari, Akiomi Nagasaka, Takeo Nakaya, Yuki Sugiura, Toshiaki Okuno, Tomoaki Koga, Akira Tanaka, Takehiko Yokomizo, Hitoshi Kurose

Research output: Contribution to journalArticle

Abstract

Leukotriene B4 receptor 1 (BLT1), a high-affinity G-protein-coupled receptor for leukotriene B4 (LTB4), is expressed on various inflammatory cells and plays critical roles in several inflammatory diseases. In myocardial infarction (MI), various inflammatory cells are known to be recruited to the infarcted area, but the function of BLT1 in MI is poorly understood. Here, we investigated the role of BLT1 in MI and the therapeutic effect of a BLT1 antagonist, ONO-4057, on MI. Mice with infarcted hearts showed increased BLT1 expression and LTB4 levels. BLT1-knockout mice with infarcted hearts exhibited attenuated leukocyte infiltration, proinflammatory cytokine production, and cell death, which led to reduced mortality and improved cardiac function after MI. Bone-marrow transplantation studies showed that BLT1 expressed on bone marrow-derived cells was responsible for the exacerbation of inflammation in infarcted hearts. Furthermore, ONO-4057 administration attenuated the inflammatory responses in hearts surgically treated for MI, which resulted in reduced mortality and improved cardiac function after MI. Our study demonstrated that BLT1 contributes to excessive inflammation after MI and could represent a new therapeutic target for MI.

Original languageEnglish
Pages (from-to)8749-8763
Number of pages15
JournalFASEB Journal
Volume34
Issue number6
DOIs
Publication statusPublished - Jun 1 2020

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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  • Cite this

    Horii, Y., Nakaya, M., Ohara, H., Nishihara, H., Watari, K., Nagasaka, A., Nakaya, T., Sugiura, Y., Okuno, T., Koga, T., Tanaka, A., Yokomizo, T., & Kurose, H. (2020). Leukotriene B4 receptor 1 exacerbates inflammation following myocardial infarction. FASEB Journal, 34(6), 8749-8763. https://doi.org/10.1096/fj.202000041R