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

Journal of Molecular and Cellular Cardiology
Yung-Hsin YehWei-Jan Chen

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, whic...Continue Reading

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Citations

Jan 18, 2016·The Journal of Thoracic and Cardiovascular Surgery·Feng-Chun TsaiYung-Hsin Yeh
Aug 27, 2016·Basic Research in Cardiology·Yung-Hsin YehWei-Jan Chen
Jan 14, 2017·Archives of Pharmacal Research·Jeong-Hyeon ParkMi-Kyoung Kwak
May 11, 2018·Oxidative Medicine and Cellular Longevity·Aleksandra Piechota-PolanczykAlicja Jozkowicz
Jul 28, 2020·International Journal of Molecular Sciences·Feng-Chun TsaiYung-Hsin Yeh
Apr 1, 2018·Naunyn-Schmiedeberg's Archives of Pharmacology·Huiliang QiuChunhua Ding
Sep 29, 2019·Cardiovascular Diabetology·Yi-Hsin ChanYung-Hsin Yeh
Aug 25, 2020·Oxidative Medicine and Cellular Longevity·Liangkai ChengCaiyan Wang
Aug 15, 2020·Scientific Reports·Kenji SuitaSatoshi Okumura
Mar 29, 2020·Journal of the American College of Cardiology·Andrea BaehrChristian Kupatt

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