Premium
Leukotriene B 4 receptor 1 exacerbates inflammation following myocardial infarction
Author(s) -
Horii Yuma,
Nakaya Michio,
Ohara Hiroki,
Nishihara Hiroaki,
Watari Kenji,
Nagasaka Akiomi,
Nakaya Takeo,
Sugiura Yuki,
Okuno Toshiaki,
Koga Tomoaki,
Tanaka Akira,
Yokomizo Takehiko,
Kurose Hitoshi
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.202000041r
Subject(s) - inflammation , proinflammatory cytokine , leukotriene b4 , medicine , receptor , myocardial infarction , bone marrow , leukotriene receptor , endocrinology , antagonist
Leukotriene B 4 receptor 1 (BLT1), a high‐affinity G‐protein‐coupled receptor for leukotriene B4 (LTB 4 ), 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 LTB 4 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.