期刊
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
卷 82, 期 -, 页码 84-92出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.yjmcc.2015.03.004
关键词
Atrial fibrillation; Heme oxygenase-1; Myofibril degradation; Statin
资金
- Chang Gung Research Grant Foundation [CMRPG 3A0641-3, 3B0211-3, 3B1691-3, 3D1371]
- National Science Council [NSC100-2314-B-182-051]
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.
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