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GPR55 Regulates Progression of Atherosclerosis by Monocyte Adhesion to Vascular Endothelium
Author(s) -
Lee Seung-Jin,
Im Dong-Soon
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/fasebj.2020.34.s1.09071
Subject(s) - monocyte , microbiology and biotechnology , cell adhesion molecule , endothelium , cell adhesion , chemistry , inflammation , receptor , cancer research , adhesion , biology , immunology , endocrinology , biochemistry , organic chemistry
G‐protein coupled receptor 55 (GPR55) is an orphan G‐protein coupled receptor, which is participate in the progression of atherosclerosis. however, the underlying mechanisms are unclear. Thus, this study investigated the molecular mechanisms responsible for monocyte adhesion to the vascular endothelium, which is a key early event in macrophage foam cell formation. In in vitro study, the pharmacological GPR55 agonist, O‐1602‐induced monocyte adhesion to the endothelial cells and adhesion molecule, Mac‐1 expression were significantly attenuated by pretreatment of GPR55 antagonist, CID 164002 in monocytes. In addition, in promoter activity analysis and chromatin immunoprecipitation assays to identify transcription factors involved in O‐1602‐induced Mac‐1 expression, both AP‐1 and NF‐κB played central roles to increase Mac‐1 transcription in O‐1602‐treated monocytes. Moreover, O‐1602‐induced activations of Gq/11 proteins, CaMKK, and AKT were found to be signaling components of the monocyte adhesion to the endothelial cells and Mac‐1 expression pathway. In in vivo study, a greater number of atherosclerotic plaques formed in ApoE (−/−) mice fed a high‐fat diet than in CID 164002 pretreated ApoE (−/−) mice, indicating a pivotal role for GPR55 in preventing vascular inflammation. Based on these results, GPR55‐mediated expression of Mac‐1 in monocytes plays a pivotal role on monocyte adhesion to vascular endothelium, leading to increased foam cell formation in the development of atherosclerosis.