Eicosapentaenoic acid prevents the progression of intracranial aneurysms in rats

Journal of Neuroinflammation

Tomohiro Aoki¹  Mika Kushamae¹  Isao Ono¹  Haruka Miyata¹  Hirokazu Koseki¹  Mieko Oka¹  Yu Abekura¹  Kampei Shimizu¹  Katsumi Takizawa²  Akira Ishii³  Susumu Miyamoto³  Hiroharu Kataoka³  Akitsugu Kawashima⁴ 

[1]Department of Molecular Pharmacology, Research Institute, National Cerebral and Cardiovascular Center

[2]Department of Neurosurgery, Asahikawa Red Cross Hospital

[3]Department of Neurosurgery, Kyoto University Graduate School of Medicine

[4]Department of Neurosurgery, Tokyo Women’s Medical University Yachiyo Medical Center

关键词: Intracranial aneurysm;    Eicosapentaenoic acid;    GPR120;   

DOI  :  10.1186/s12974-020-01802-8

来源: DOAJ

【 摘 要 】

Abstract 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 using EPA to prevent the progression of IAs.

【 授权许可】

Unknown