ID | 115483 |
タイトル別表記 | Pitavastatin and Vascular Stress
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著者 |
Mitsuhashi, Takeshi
Tokushima University
Uemoto, Ryoko
Tokushima University
Ishikawa, Kazue
Tokushima University
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キーワード | Pitavastatin
Pleiotropic effect
Atherogenesis
Ischemia
eNOS
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資料タイプ |
学術雑誌論文
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抄録 | Aim: Statins have a protective impact against cardiovascular diseases through not only lipid-lowering effects but also pleiotropic effects, including activation of the endothelial nitric oxide synthase (eNOS) system. We aimed to clarify the protective effects of a statin against atherogenesis and ischemia in eNOS-/- mice.
Methods: Study 1. eNOS-/- Apolipoprotein E (ApoE)-/- mice were treated with a vehicle or pitavastatin (0.3 mg/kg/day) for 4 weeks. Study 2. eNOS-/- mice were also treated with a vehicle or the same dose of pitavastatin for 2 weeks prior to hind-limb ischemia. Results: In Study 1, pitavastatin attenuated plaque formation and medial fibrosis of the aortic root with decreased macrophage infiltration in eNOS-/- ApoE-/- mice. PCR array analysis showed reductions in aortic gene expression of proatherogenic factors, including Ccl2 and Ccr2 in pitavastatin-treated double mutant mice. In addition, pitavastatin activated not only atherogenic p38MAPK and JNK but also anti-atherogenic ERK1/2 and ERK5 in the aorta of the double mutant mice. In Study 2, pitavastatin prolonged hind-limb survival after the surgery with increased BCL2-to-BAX protein ratio and inactivated JNK. Enhanced expression of anti-apoptotic genes, including Vegf, Api5, Atf5, Prdx2, and Dad1, was observed in the ischemic limb of pitavastatin-treated eNOS-/- mice. Furthermore, pitavastatin activated both aortic and skeletal muscle AMPK in the eNOS-deficient vascular injury models. Conclusion: Pitavastatin exerts eNOS-independent protective effects against atherogenesis and hind-limb ischemia in mice, which may occur via modifications on key molecules such as AMPK and diverse molecules. |
掲載誌名 |
Journal of Atherosclerosis and Thrombosis
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ISSN | 18803873
13403478
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出版者 | Japan Atherosclerosis Society
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巻 | 25
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号 | 1
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開始ページ | 65
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終了ページ | 80
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発行日 | 2018-01-01
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権利情報 | Copyright©2018 Japan Atherosclerosis Society
This article is distributed under the terms of the latest version of CC BY-NC-SA defined by the Creative Commons Attribution License.(https://creativecommons.org/licenses/by-nc-sa/4.0/) |
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言語 |
eng
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出版社版
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部局 |
医学系
先端酵素学研究所
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