Rosuvastatin suppresses atrial tachycardia-induced cellular remodeling via Akt/Nrf2/heme oxygenase-1 pathway.
J Mol Cell Cardiol
; 82: 84-92, 2015 May.
Article
em En
| MEDLINE
| ID: mdl-25771143
ABSTRACT
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.
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Base de dados:
MEDLINE
Assunto principal:
Taquicardia Atrial Ectópica
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Transdução de Sinais
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Inibidores de Hidroximetilglutaril-CoA Redutases
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Miócitos Cardíacos
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Heme Oxigenase-1
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Proteínas Proto-Oncogênicas c-akt
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Fator 2 Relacionado a NF-E2
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Rosuvastatina Cálcica
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article