○種別 (必須): | □ | 学術論文 (審査論文)
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○言語 (必須): | □ | 英語
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○招待 (推奨): |
○審査 (推奨): |
○カテゴリ (推奨): | □ | 研究
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○共著種別 (推奨): |
○学究種別 (推奨): | □ | 博士課程学生による研究報告
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○組織 (推奨): | 1. | 徳島大学.医学研究科.医科学専攻 (2004年4月1日〜)
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○著者 (必須): | 1. | 多田 恵曜 ([徳島大学.大学院医歯薬学研究部.医学域.先端医学教育研究プロジェクト]/[徳島大学.大学院医歯薬学研究部.医学域.医科学部門.外科系.脳神経外科学])
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| 2. | (英) Kitazato T. Keiko (日) 北里 慶子 (読) きたざと けいこ
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| 3. | 八木 謙次
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| 4. | 島田 健司 ([徳島大学.病院.先端医科医療開発研究プロジェクト]/[徳島大学.病院.診療科.脳·神経·精神科.脳神経外科])
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○学籍番号 (推奨): |
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| 5. | 松下 展久
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○学籍番号 (推奨): | □ | ****
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| 6. | 木内 智也
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| 7. | 兼松 康久
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| 8. | 里見 淳一郎
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| 9. | 影治 照喜
○役割 (任意): |
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| 10. | 永廣 信治
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○題名 (必須): | □ | (英) Statins Promote the Growth of Experimentally Induced Cerebral Aneurysms in Estrogen-Deficient Rats (日)
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○副題 (任意): |
○要約 (任意): | □ | (英) The pathogenesis of cerebral aneurysms is linked to inflammation, degradation of the extracellular matrix, and vascular wall apoptosis. Statins exert pleiotropic effects on the vasculature, independent of their cholesterol-lowering properties. To explore the detailed pathogenesis of cerebral aneurysms, we examined their progression in a rat model and studied whether statins prevent their initiation and growth. Cerebral aneurysms were induced in female rats subjected to hypertension, increased hemodynamic stress, and estrogen deficiency. The development of aneurysm was assessed morphologically on corrosion casts. The effects of pravastatin (5, 25, or 50 mg/kg per day) and of simvastatin (5 mg/kg per day) on their aneurysms were studied. Human brain endothelial cells were also used to determine the effects of pravastatin. Pravastatin (5 mg/kg per day) reduced endothelial damage and inhibited aneurysm formation; there was an association with increased endothelial nitric oxide synthase (eNOS) levels and a decrease in human brain endothelial cell adhesion molecules. Unexpectedly, 25 mg/kg per day and 50 mg/kg per day pravastatin and 5 mg/kg per day simvastatin promoted aneurysmal growth, and high-dose pravastatin induced aneurysmal rupture. The deleterious effects exerted by these statins were associated with an increase in apoptotic caspase-3 levels and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells, suggesting that statins exert bidirectional effects. Our results provide the first evidence that cerebral aneurysm growth is partly associated with apoptosis and issue a warning that statins exert bidirectional effects on cerebral aneurysms. Additional intensive research is necessary to understand better their mechanisms and to identify patients in whom the administration of statins may elicit deleterious effects. (日)
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○キーワード (推奨): | 1. | (英) Animals (日) (読)
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| 2. | (英) Apoptosis (日) (読)
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| 3. | (英) Brain (日) (読)
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| 4. | (英) Cells, Cultured (日) (読)
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| 5. | (英) Disease Models, Animal (日) (読)
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| 6. | (英) Endothelial Cells (日) (読)
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| 7. | (英) Estrogens (日) (読)
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| 8. | (英) Female (日) (読)
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| 9. | (英) Humans (日) (読)
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| 10. | (英) Hydroxymethylglutaryl-CoA Reductase Inhibitors (日) (読)
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| 11. | (英) Hypertension (日) (読)
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| 12. | (英) Intracranial Aneurysm (日) (読)
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| 13. | (英) Nitric Oxide Synthase Type III (日) (読)
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| 14. | (英) Pravastatin (日) (読)
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| 15. | (英) Rats (日) (読)
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| 16. | (英) Rats, Sprague-Dawley (日) (読)
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| 17. | (英) Simvastatin (日) (読)
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○発行所 (推奨): |
○誌名 (必須): | □ | Stroke ([American Heart Association])
(pISSN: 0039-2499, eISSN: 1524-4628)
○ISSN (任意): | □ | 1524-4628
ISSN: 0039-2499
(pISSN: 0039-2499, eISSN: 1524-4628) Title: StrokeTitle(ISO): StrokePublisher: American Heart Association (NLM Catalog)
(Scopus)
(CrossRef)
(Scopus information is found. [need login])
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○巻 (必須): | □ | 42
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○号 (必須): | □ | 8
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○頁 (必須): | □ | 2286 2293
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○都市 (任意): |
○年月日 (必須): | □ | 西暦 2011年 7月 7日 (平成 23年 7月 7日)
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○URL (任意): |
○DOI (任意): | □ | 10.1161/STROKEAHA.110.608034 (→Scopusで検索)
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○PMID (任意): | □ | 21737796 (→Scopusで検索)
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○備考 (任意): | 1. | (英) Article.Affiliation: Department of Neurosurgery, Institute of Health Biosciences, The University of Tokushima, Tokushima City, Japan. yoshiteru.tada@hotmail.co.jp (日)
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| 2. | (英) Article.PublicationTypeList.PublicationType: Journal Article (日)
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| 3. | (英) Article.PublicationTypeList.PublicationType: Research Support, Non-U.S. Gov't (日)
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