徳島大学 教育・研究者情報データベース(EDB)

1. 八木 秀介([徳島大学.大学院医歯薬学研究部.医学域.連携研究部門(医学域).寄附講座系(医学域).地域医療人材育成(医学域)])

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2. 赤池 雅史([徳島大学.大学院医歯薬学研究部.医学域.医科学部門.社会医学系.医療教育学])

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3. 粟飯原 賢一([徳島大学.大学院医歯薬学研究部.医学域.連携研究部門(医学域).寄附講座系(医学域).実践地域診療・医科学])

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4. (英) Ishikawa Kazue

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5. 岩瀬 俊

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6. 池田 康将([徳島大学.大学院医歯薬学研究部.医学域.医科学部門.生理系.薬理学]/[徳島大学.医学部.医学科.病態情報医学講座.薬理学分野]/[徳島大学.医科学教育部.医学専攻.病態情報医学講座]/[徳島大学.大学院医歯薬学研究部.医学域.医科学部門.生理系.薬理学])

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7. 添木 武([徳島大学.大学院医歯薬学研究部.医学域.連携研究部門(医学域).寄附講座系(医学域).実践地域診療・医科学])

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8. 吉田 守美子([徳島大学.大学院医歯薬学研究部.医学域.医科学部門.内科系.血液・内分泌代謝内科学])

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9. (英) Sumitomo-Ueda Yuka

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10. 松本 俊夫

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11. 佐田 政隆([徳島大学.大学院医歯薬学研究部.医学域.医科学部門.内科系.循環器内科学])

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(英) Endothelial nitric oxide synthase-independent protective action of statin against angiotensin II-induced atrial remodeling via reduced oxidant injury.

(英) Activation of the renin-angiotensin system exacerbates atrial remodeling, leading to atrial fibrillation and thrombosis, especially in a condition with decreased NO bioavailability. Recently, it has been reported that statins reduce the incidence of atrial fibrillation through attenuation of atrial remodeling; however, the mechanisms have not been completely elucidated. Therefore, we aimed to clarify the beneficial effect of statin on atrial remodeling in condition with reduced NO bioavailability. Endothelial NO synthase(-/-) mice were sham operated or infused with angiotensin II (Ang II) via an osmotic minipump for 2 weeks, and Ang II-infused mice were divided into 3 treatment groups: pitavastatin, Tempol (a free radical scavenger), or vehicle. Echocardiography and electrocardiography showed that Ang II infusion caused left atrial enlargement and a high incidence of atrial fibrillation, whereas pitavastatin and Tempol prevented these abnormalities. In histological analysis, Ang II-induced atrial interstitial fibrosis, perivascular fibrosis, and cardiomyocyte hypertrophy were all attenuated by pitavastatin and Tempol. Immunohistochemical staining showed that Ang II downregulated thrombomodulin and tissue factor pathway inhibitor and upregulated tissue factor and plasminogen activator inhibitor 1 in the left atrium and that pitavastatin and Tempol corrected the thrombogenic condition. Moreover, pitavastatin and Tempol reduced Ang II-induced atrial superoxide production and atrial transforming growth factor-beta1 expression and Smad 2/3 phosphorylation. Atrial rac1-GTPase activity, known to activate NADPH oxidase, was attenuated by pitavastatin but not by Tempol. In conclusion, pitavastatin exerts endothelial NO synthase-independent protective actions against Ang II-induced atrial remodeling and atrial fibrillation with enhanced thrombogenicity through suppression of oxidant injury.

1. (英) Analysis of Variance
2. (英) Angiotensin II
3. (英) Animals
4. (英) Antioxidants
5. (英) Atrial Fibrillation
6. (英) Blood Pressure
7. (英) Blotting, Western
8. (英) Cardiomegaly
9. (英) Cyclic N-Oxides
10. (英) Echocardiography
11. (英) Fibrosis
12. (英) Heart Atria
13. (英) Heart Rate
14. (英) Hydroxymethylglutaryl-CoA Reductase Inhibitors
15. (英) Male
16. (英) Mice
17. (英) Mice, Knockout
18. (英) Myocytes, Cardiac
19. (英) Nitric Oxide Synthase Type III
20. (英) Oxidative Stress
21. (英) Quinolines
22. (英) Renin-Angiotensin System
23. (英) Reverse Transcriptase Polymerase Chain Reaction
24. (英) Signal Transduction
25. (英) Smad2 Protein
26. (英) Smad3 Protein
27. (英) Spin Labels
28. (英) Transforming Growth Factor beta1

1. (英) Affiliation: Department of Cardiovascular Medicine, University of Tokushima Graduate School of Health Biosciences, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan. syagi@clin.med.tokushima-u.ac.jp.

2. (英) PublicationType: Journal Article

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