Rosuvastatin suppresses atrial tachycardia-induced cellular remodeling via Akt/Nrf2/heme oxygenase-1 pathway

被引：60

作者：

Yeh, Yung-Hsin ^{[1
]}

Kuo, Chi-Tai ^{[1
]}

Chang, Gwo-Jyh ^{[2
]}

Chen, Ying-Hwa ^{[5
]}

Lai, Ying-Ju ^{[3
]}

Cheng, Mei-Ling ^{[4
]}

Chen, Wei-Jan ^{[1
]}

机构：

[1] Chang Gung Univ, Chang Gung Mem Hosp, Cardiovasc Div, Coll Med, Taoyuan 333, Taiwan

[2] Chang Gung Univ, Grad Inst Clin Med Sci, Coll Med, Taoyuan 333, Taiwan

[3] Chang Gung Univ, Dept Resp Therapy, Coll Med, Taoyuan 333, Taiwan

[4] Chang Gung Univ, Dept Biomed Sci, Coll Med, Taoyuan 333, Taiwan

[5] Natl Yang Ming Univ, Div Cardiol, Dept Internal Med, Taipei Vet Gen Hosp,Coll Med, Taipei, Taiwan

来源：

JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY | 2015年 / 82卷

关键词：

Atrial fibrillation; Heme oxygenase-1; Myofibril degradation; Statin; HEME OXYGENASE-1; OXIDATIVE STRESS; OXIDASE ACTIVITY; FIBRILLATION; EXPRESSION; ACTIVATION; MECHANISMS; KINASE; SIMVASTATIN; SUPEROXIDE;

D O I：

10.1016/j.yjmcc.2015.03.004

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Atrial fibrillation (AF) is associated with structural remodeling in atrial myocytes. Emerging evidence suggests that statin has a protective effect on AF through cholesterol-independent mechanisms. The aim of this study is to investigate whether heme oxygenase-1 (HO-1), a potent antioxidant system, mediates the suppressive effect of statin on atrial tachycardia-induced structural remodeling. Treatment of cultured atrium-derived myocytes (HL-1 cell line) with rosuvastatin enhanced HO-1 expression/activity and attenuated tachypacing-induced oxidative stress and myofibril degradation. Heme oxygenase-1 inhibitors and small-interfering RNA for HO-1 blocked the inhibitory effect of rosuvastatin on tachypacing-stimulated changes, suggesting the crucial role of HO-1 in mediating the effect of rosuvastatin. Time-dependent experiments and loss-of-function study demonstrated that Akt/NrF2 pathways lay to the up-stream of HO-1 in this signaling cascade. Furthermore, the involvement of Akt/Nrf2/HO-1 pathway in the antioxidant effect of rosuvastatin was documented in an ex vivo tachypacing model. The suppressive effect of statin on atrial tachypacing-induced cellular remodeling is mediated via the activation of Akt/Nrf2/HO-1 signaling, which provides a possible explanation for the protective effect of statin on AF. (C) 2015 Elsevier Ltd. All rights reserved.

引用

页码：84 / 92

页数：9

共 42 条

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