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Effects of atorvastatin on calcium-regulating proteins: a possible mechanism to repair cardiac dysfunction in spontaneously hypertensive rats

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Abstract

Previous clinical and experimental studies have demonstrated that statins, the inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, can improve left ventricular function in damaged hearts. Also, the normal expression of Ca2+ regulatory proteins is critical for efficient myocardial function. However, it is still unclear whether the beneficial effect of statins on cardiac function is associated with alterations of Ca2+ regulatory proteins. In this study, we investigated the effect of atorvastatin on cardiac function in spontaneously hypertensive rats (SHRs), focusing in particular on its impact on the expression of sarcoplasmic reticulum Ca2+-adenosine triphosphatase (SERCA2a), phospholamban (PLB) and its phosphorylated form (phosphorylated PLB), all of which are Ca2+ regulatory proteins in myocardium. SHRs showed decreases in gene expression of SERCA2a and phosphorylated PLB, and reduction in SERCA activity in the left ventricular myocardium, as well as reduced cardiac function, compared to age-matched Wistar Kyoto rats (WKYs). Furthermore, we showed that in SHRs atorvastatin preserved cardiac dysfunction accompanied by positive alterations in calcium regulatory proteins, with up-regulation in expression of SERCA2a and phosphorylated PLB, and with improvement of SERCA activity. Thus, atorvastatin has positive effects on calcium regulatory proteins, which may be one of the mechanisms of the beneficial effect of statins on cardiac function in spontaneously hypertensive rats.

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Acknowledgments

We express our sincere gratitude to Dr. Iain C. Bruce for revising this manuscript. This research was supported by the National Natural Science Foundation of China (Grant No. 30470715), the Research Fund for the Doctoral Program of Higher Education of China (No. 20040335118), and the Research Fund of the Health Agency of Zhejiang Province (No. 2007A078), and was supported in part by the E-Institute of Shanghai Municipal Education Commission of China (No. E-04010).

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Authors and Affiliations

  1. Institute of Cardiology, The First Affiliated Hospital, College of Medicine, Zhejiang University, #79, Qingchun Road, Hangzhou, 310003, P.R.China

    Lei Yao, Guo-Ping Chen, Xian Lu, Liang-Rong Zheng, Yun Mou & Shen-Jiang Hu (Prof.)

  2. Division of Nitric Oxide and Inflammatory Medicine, E-Institute of Shanghai Universities, Shanghai, P.R.China

    Shen-Jiang Hu (Prof.)

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  1. Lei Yao
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  2. Guo-Ping Chen
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Correspondence to Shen-Jiang Hu.

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Returned for 1. Revision: 7 January 2008 1. Revision received: 25 July 2008

Returned for 2. Revision: 11 August 2008 2. Revision received: 8 September 2008

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Yao, L., Chen, GP., Lu, X. et al. Effects of atorvastatin on calcium-regulating proteins: a possible mechanism to repair cardiac dysfunction in spontaneously hypertensive rats. Basic Res Cardiol 104, 258–268 (2009). https://doi.org/10.1007/s00395-008-0751-y

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  • DOI: https://doi.org/10.1007/s00395-008-0751-y

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