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Eicosapentaenoic acid prevents the progression of intracranial aneurysms in rats.
J Neuroinflammation. 2020 Apr 24; 17(1):129.JN

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.

Authors+Show Affiliations

Department of Molecular Pharmacology, Research Institute, National Cerebral and Cardiovascular Center, Suita, Osaka, 564-8565, Japan. Department of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto, Japan. Core Research for Evolutional Science and Technology (CREST) from Japan Agency for Medical Research and Development (AMED), National Cerebral and Cardiovascular Center, Osaka, Japan.Department of Molecular Pharmacology, Research Institute, National Cerebral and Cardiovascular Center, Suita, Osaka, 564-8565, Japan. Department of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto, Japan. Core Research for Evolutional Science and Technology (CREST) from Japan Agency for Medical Research and Development (AMED), National Cerebral and Cardiovascular Center, Osaka, Japan.Department of Neurosurgery, Tokyo Women's Medical University Yachiyo Medical Center, Chiba, Japan.Department of Neurosurgery, Asahikawa Red Cross Hospital, Hokkaido, Japan.Department of Molecular Pharmacology, Research Institute, National Cerebral and Cardiovascular Center, Suita, Osaka, 564-8565, Japan. Core Research for Evolutional Science and Technology (CREST) from Japan Agency for Medical Research and Development (AMED), National Cerebral and Cardiovascular Center, Osaka, Japan. Department of Neurosurgery, The JIKEI University Hospital, Tokyo, Japan.Department of Molecular Pharmacology, Research Institute, National Cerebral and Cardiovascular Center, Suita, Osaka, 564-8565, Japan. Core Research for Evolutional Science and Technology (CREST) from Japan Agency for Medical Research and Development (AMED), National Cerebral and Cardiovascular Center, Osaka, Japan. Department of Neurosurgery, Shiga University of Medical Science, Shiga, Japan.Department of Molecular Pharmacology, Research Institute, National Cerebral and Cardiovascular Center, Suita, Osaka, 564-8565, Japan. Department of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto, Japan. Core Research for Evolutional Science and Technology (CREST) from Japan Agency for Medical Research and Development (AMED), National Cerebral and Cardiovascular Center, Osaka, Japan.Department of Molecular Pharmacology, Research Institute, National Cerebral and Cardiovascular Center, Suita, Osaka, 564-8565, Japan. Core Research for Evolutional Science and Technology (CREST) from Japan Agency for Medical Research and Development (AMED), National Cerebral and Cardiovascular Center, Osaka, Japan. Department of Neurosurgery, Tokyo Women's Medical University, Tokyo, Japan.Department of Molecular Pharmacology, Research Institute, National Cerebral and Cardiovascular Center, Suita, Osaka, 564-8565, Japan. Core Research for Evolutional Science and Technology (CREST) from Japan Agency for Medical Research and Development (AMED), National Cerebral and Cardiovascular Center, Osaka, Japan. Department of Neurosurgery, Showa University, Tokyo, Japan.Department of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.Department of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.Department of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.Department of Molecular Pharmacology, Research Institute, National Cerebral and Cardiovascular Center, Suita, Osaka, 564-8565, Japan. tomoaoki@ncvc.go.jp. Core Research for Evolutional Science and Technology (CREST) from Japan Agency for Medical Research and Development (AMED), National Cerebral and Cardiovascular Center, Osaka, Japan. tomoaoki@ncvc.go.jp.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32331514

Citation

Abekura, Yu, et al. "Eicosapentaenoic Acid Prevents the Progression of Intracranial Aneurysms in Rats." Journal of Neuroinflammation, vol. 17, no. 1, 2020, p. 129.
Abekura Y, Ono I, Kawashima A, et al. Eicosapentaenoic acid prevents the progression of intracranial aneurysms in rats. J Neuroinflammation. 2020;17(1):129.
Abekura, Y., Ono, I., Kawashima, A., Takizawa, K., Koseki, H., Miyata, H., Shimizu, K., Oka, M., Kushamae, M., Miyamoto, S., Kataoka, H., Ishii, A., & Aoki, T. (2020). Eicosapentaenoic acid prevents the progression of intracranial aneurysms in rats. Journal of Neuroinflammation, 17(1), 129. https://doi.org/10.1186/s12974-020-01802-8
Abekura Y, et al. Eicosapentaenoic Acid Prevents the Progression of Intracranial Aneurysms in Rats. J Neuroinflammation. 2020 Apr 24;17(1):129. PubMed PMID: 32331514.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Eicosapentaenoic acid prevents the progression of intracranial aneurysms in rats. AU - Abekura,Yu, AU - Ono,Isao, AU - Kawashima,Akitsugu, AU - Takizawa,Katsumi, AU - Koseki,Hirokazu, AU - Miyata,Haruka, AU - Shimizu,Kampei, AU - Oka,Mieko, AU - Kushamae,Mika, AU - Miyamoto,Susumu, AU - Kataoka,Hiroharu, AU - Ishii,Akira, AU - Aoki,Tomohiro, Y1 - 2020/04/24/ PY - 2019/12/19/received PY - 2020/04/02/accepted PY - 2020/4/26/entrez PY - 2020/4/26/pubmed PY - 2020/4/26/medline KW - Eicosapentaenoic acid KW - GPR120 KW - Intracranial aneurysm SP - 129 EP - 129 JF - Journal of neuroinflammation JO - J Neuroinflammation VL - 17 IS - 1 N2 - 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. SN - 1742-2094 UR - https://www.unboundmedicine.com/medline/citation/32331514/Eicosapentaenoic_acid_prevents_the_progression_of_intracranial_aneurysms_in_rats L2 - https://jneuroinflammation.biomedcentral.com/articles/10.1186/s12974-020-01802-8 DB - PRIME DP - Unbound Medicine ER -
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