Hyperhomocysteinemia induced by excessive methionine intake promotes rupture of cerebral aneurysms in ovariectomized rats

• Material Type: 博士論文
• Title: Hyperhomocysteinemia induced by excessive methionine intake promotes rupture of cerebral aneurysms in ovariectomized rats
• Author/Editor: Korai, Masaaki; Kitazato, Keiko T.; Tada, Yoshiteru; Miyamoto, Takeshi; Shimada, Kenji; Matsushita, Nobuhisa; Kanematsu, Yasuhisa; Satomi, Junichiro; Hashimoto, Tomoki; Nagahiro, Shinji
• Author Heading: Korai, Masaaki; Kitazato, Keiko T.; Tada, Yoshiteru; Miyamoto, Takeshi; Shimada, Kenji; Matsushita, Nobuhisa; Kanematsu, Yasuhisa; Satomi, Junichiro; Hashimoto, Tomoki; Nagahiro, Shinji
• Publication, Distribution, etc.: Springer nature
• Publication Date: 2016-06-27
• Publication Date (W3CDTF): 2016-06-27
• Alternative Title: メチオニン過剰摂取により誘導された高ホモシステイン血症は卵巣摘出ラットにおける脳動脈瘤破裂を促進する
• Periodical title: Journal of Neuroinflammation
• No. or year of volume/issue: 13
• Volume: 13
• Pages: 165-
• ISSN (Periodical Title): ISSN : 1742-2094
• Degree grantor/type: 徳島大学
• Date Granted: 2017-01-26
• Dissertation Number: 甲第3006号
• Degree Type: 博士（医学）
• Text Language Code: eng
• Subject Heading: Cerebral aneurysm; Hyperhomocysteinemia; Methionine; Matrix metalloproteinase-9; Folic acid; Cerebral aneurysm rupture; Anterior communicating artery; Macrophage; Tissue inhibitor of metalloproteinase-2
• Target Audience: 一般
• Note (General): Background: Hyperhomocysteinemia (HHcy) is associated with inflammation and a rise in the expression of matrix metalloproteinase-9 (MMP-9) in the vascular wall. However, the role of HHcy in the growth and rupture of cerebral aneurysms remains unclear. Methods: Thirteen-week-old female Sprague-Dawley rats were subject to bilateral ovariectomy and ligation of the right common carotid artery and fed an 8 % high-salt diet to induce cerebral aneurysms. Two weeks later, they underwent ligation of the bilateral posterior renal arteries. They were divided into two groups and methionine (MET) was or was not added to their drinking water. In another set of experiments, the role of folic acid (FA) against cerebral aneurysms was assessed. Results: During a 12-week observation period, subarachnoid hemorrhage due to aneurysm rupture was observed at the anterior communicating artery (AcomA) or the posterior half of the circle of Willis. HHcy induced by excessive MET intake significantly increased the incidence of ruptured aneurysms at 6–8 weeks. At the AcomA of rats treated with MET, we observed the promotion of aneurysmal growth and infiltration by M1 macrophages. Furthermore, the mRNA level of MMP-9, the ratio of MMP-9 to the tissue inhibitor of metalloproteinase-2, and the level of interleukin-6 were higher in these rats. Treatment with FA abolished the effect of MET, suggesting that the inflammatory response and vascular degradation at the AcomA is attributable to HHcy due to excessive MET intake. Conclusions: We first demonstrate that in hypertensive ovariectomized rats, HHcy induced by excessive MET intake may be associated with the propensity of the aneurysm wall to rupture.
• Format (IMT): application/pdf
• Source: fulltext; https://repo.lib.tokushima-u.ac.jp/files/public/11/110031/20170929142249133901/LID201704111001.pdf; https://repo.lib.tokushima-u.ac.jp/files/public/11/110031/20170929142249431244/LID201704111002.pdf
• Access Restrictions: インターネット公開
• Rights (production): Copyright: © 2016 Korai et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
• Related Material (DOI): 10.1186/s12974-016-0634-3
• Periodical Title (NCID): AA12051048; https://ci.nii.ac.jp/ncid/AA12051048
• Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）; https://irdb.nii.ac.jp
• Original Data Provider (Database): 徳島大学 : 徳島大学機関リポジトリ