徳島大学 教育・研究者情報データベース(EDB)

1. 徳島大学.医学研究科.医科学専攻(2004年4月1日〜)

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.中央診療施設等.地域脳神経外科診療部])

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5. 松下 展久

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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

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10. 永廣 信治

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(英) Statins Promote the Growth of Experimentally Induced Cerebral Aneurysms in Estrogen-Deficient Rats

(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.

1. (英) Animals
2. (英) Apoptosis
3. (英) Brain
4. (英) Cells, Cultured
5. (英) Disease Models, Animal
6. (英) Endothelial Cells
7. (英) Estrogens
8. (英) Female
9. (英) Humans
10. (英) Hydroxymethylglutaryl-CoA Reductase Inhibitors
11. (英) Hypertension
12. (英) Intracranial Aneurysm
13. (英) Nitric Oxide Synthase Type III
14. (英) Pravastatin
15. (英) Rats
16. (英) Rats, Sprague-Dawley
17. (英) Simvastatin

1. (英) Article.Affiliation: Department of Neurosurgery, Institute of Health Biosciences, The University of Tokushima, Tokushima City, Japan. yoshiteru.tada@hotmail.co.jp

2. (英) Article.PublicationTypeList.PublicationType: Journal Article

3. (英) Article.PublicationTypeList.PublicationType: Research Support, Non-U.S. Gov't