Akitsugu Kawashima    Department   School of Medicine(Tokyo Women's Medical University Hospital), School of Medicine    Position   Associate Professor
Article types	Original article
Language	English
Peer review	Peer reviewed
Title	Eicosapentaenoic acid prevents the progression of intracranial aneurysms in rats.
Journal	Formal name：Journal of neuroinflammation Abbreviation：J Neuroinflammation ISSN code：17422094/17422094
Domestic / Foregin	Foregin
Volume, Issue, Page	17(1),pp.129
Author and coauthor	Abekura Yu, Ono Isao, Kawashima Akitsugu, Takizawa Katsumi, Koseki Hirokazu, Miyata Haruka, Shimizu Kampei, Oka Mieko, Kushamae Mika, Miyamoto Susumu, Kataoka Hiroharu, Ishii Akira, Aoki Tomohiro
Publication date	2020/04
Summary	BACKGROUND:As subarachnoid hemorrhage due to rupture of an intracranial aneurysm (IA) has quite a poor outcome despite of an intensive medical care, development of a novel treatment targeting unruptured IAs based on the correct understanding of pathogenesis is mandatory for social health.METHODS:Using previously obtained gene expression profile data from surgically resected unruptured human IA lesions, we selected G-protein coupled receptor 120 (GPR120) as a gene whose expression is significantly higher in lesions than that in control arterial walls. To corroborate a contribution of GPR120 signaling to the pathophysiology, we used an animal model of IAs and examine the effect of a GPR120 agonist on the progression of the disease. IA lesion was induced in rats through an increase of hemodynamic stress achieved by a one-sided carotid ligation and induced hypervolemia. Eicosapentaenoic acid (EPA) was used as an agonist for GPR120 in this study and its effect on the size of IAs, the thinning of media, and infiltration of macrophages in lesions were examined.RESULT:EPA administered significantly suppressed the size of IAs and the degenerative changes in the media in rats. EPA treatment also inhibited infiltration of macrophages, a hallmark of inflammatory responses in lesions. In in vitro experiments using RAW264.7 cells, pre-treatment of EPA partially suppressed lipopolysaccharide-induced activation of nuclear factor-kappa B and also the transcriptional induction of monocyte chemoattractant protein 1 (MCP-1), a major chemoattractant for macrophages to accumulate in lesions. As a selective agonist of GPR120, TUG-891, could reproduce the effect of EPA in RAW264.7 cells, EPA presumably acted on this receptor to suppress inflammatory responses. Consistently, EPA remarkably suppressed MCP-1 expression in lesions, suggesting the in vivo relevance of in vitro studies.CONCLUSIONS:These results combined together suggest the potential of the medical therapy targeting GPR120 or us
DOI	10.1186/s12974-020-01802-8
PMID	32331514