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カワシマ アキツグ
Kawashima Akitsugu
川島 明次 所属 医学部 医学科（東京女子医科大学病院） 職種 准教授 |
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| 論文種別 | 原著 |
| 言語種別 | 英語 |
| 査読の有無 | 査読あり |
| 表題 | Eicosapentaenoic acid prevents the progression of intracranial aneurysms in rats. |
| 掲載誌名 | 正式名：Journal of neuroinflammation 略 称：J Neuroinflammation ISSNコード：17422094/17422094 |
| 掲載区分 | 国外 |
| 巻・号・頁 | 17(1),pp.129 |
| 著者・共著者 | 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 |
| 発行年月 | 2020/04 |
| 概要 | 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 |