• Open Access

Rosuvastatin-attenuated heart failure in aged spontaneously hypertensive rats via PKCα/β2 signal pathway

Authors

  • Zhaohui Qiu,

    1. Shanghai Institute of Cardiovascular Diseases of Zhongshan Hospital, Fudan University, Shanghai, China
    2. Institute of Biomedical Science, Fudan University, Shanghai, China
    3. Huadong Hospital, Fudan University, Shanghai, China
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    • These authors contributed equally to this work.
  • Wenbin Zhang,

    1. Shanghai Institute of Cardiovascular Diseases of Zhongshan Hospital, Fudan University, Shanghai, China
    2. Institute of Biomedical Science, Fudan University, Shanghai, China
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    • These authors contributed equally to this work.
  • Fan Fan,

    1. Shanghai Institute of Cardiovascular Diseases of Zhongshan Hospital, Fudan University, Shanghai, China
    2. Institute of Biomedical Science, Fudan University, Shanghai, China
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  • Hua Li,

    1. Shanghai Institute of Cardiovascular Diseases of Zhongshan Hospital, Fudan University, Shanghai, China
    2. Institute of Biomedical Science, Fudan University, Shanghai, China
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  • Chaoneng Wu,

    1. Shanghai Institute of Cardiovascular Diseases of Zhongshan Hospital, Fudan University, Shanghai, China
    2. Institute of Biomedical Science, Fudan University, Shanghai, China
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  • Yong Ye,

    1. Institute of Biomedical Science, Fudan University, Shanghai, China
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  • Qijun Du,

    1. Shanghai Institute of Cardiovascular Diseases of Zhongshan Hospital, Fudan University, Shanghai, China
    2. Institute of Biomedical Science, Fudan University, Shanghai, China
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  • Zheng Li,

    1. Zhongshan Hospital, Fudan University, Shanghai, China
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  • Xiaona Hu,

    1. Huadong Hospital, Fudan University, Shanghai, China
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  • Gang Zhao,

    1. Shanghai Institute of Cardiovascular Diseases of Zhongshan Hospital, Fudan University, Shanghai, China
    2. Institute of Biomedical Science, Fudan University, Shanghai, China
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  • Aijun Sun,

    1. Shanghai Institute of Cardiovascular Diseases of Zhongshan Hospital, Fudan University, Shanghai, China
    2. Institute of Biomedical Science, Fudan University, Shanghai, China
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  • Zhijun Bao,

    1. Huadong Hospital, Fudan University, Shanghai, China
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  • Junbo Ge

    Corresponding author
    1. Institute of Biomedical Science, Fudan University, Shanghai, China
    • Shanghai Institute of Cardiovascular Diseases of Zhongshan Hospital, Fudan University, Shanghai, China
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Correspondence to: Junbo GE, M.D., Shanghai Institute of Cardiovascular Diseases of Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China.

Tel.: +86 21 64041990 (ext. 2152)

Fax: +86 21 64223006

E-mail: Ge.junbo@zs-hospital.sh.cn

Abstract

There are controversies concerning the capacity of Rosuvastatin to attenuate heart failure in end-stage hypertension. The aim of the study was to show whether the Rosuvastatin might be effective or not for the heart failure treatment. Twenty-one spontaneously hypertensive rats (SHRs) aged 52 weeks with heart failure were randomly divided into three groups: two receiving Rosuvastatin at 20 and 40 mg/kg/day, respectively, and the third, placebo for comparison with seven Wistar-Kyoto rats (WKYs) as controls. After an 8-week treatment, the systolic blood pressure (SBP) and echocardiographic features were evaluated; mRNA level of B-type natriuretic peptide (BNP) and plasma NT-proBNP concentration were measured; the heart tissues were observed under electron microscope (EM); myocardial sarcoplasmic reticulum Ca2+ pump (SERCA-2) activity and mitochondria cytochrome C oxidase (CCO) activity were measured; the expressions of SERCA-2a, phospholamban (PLB), ryanodine receptor2 (RyR2), sodium–calcium exchanger 1 (NCX1), Ca2+/calmodulin-dependent protein kinase II (CaMKII) and protein phosphatase inhibitor-1 (PPI-1) were detected by Western blot and RT-qPCR; and the total and phosphorylation of protein kinase Cα/β (PKCα/β) were measured. Aged SHRs with heart failure was characterized by significantly decreased left ventricular ejection fraction and left ventricular fraction shortening, enhanced left ventricular end-diastolic diameter and LV Volume, accompanied by increased plasma NT-proBNP and elevated BNP gene expression. Damaged myofibrils, vacuolated mitochondria and swollen sarcoplasmic reticulum were observed by EM. Myocardium mitochondria CCO and SERCA-2 activity decreased. The expressions of PLB and NCX1 increased significantly with up-regulation of PPI-1 and down-regulation of CaMKII, whereas that of RyR2 decreased. Rosuvastatin was found to ameliorate the heart failure in aged SHRs and to improve changes in SERCA-2a, PLB, RyR2, NCX1, CaMKII and PPI-1; PKCα/β2 signal pathway to be suppressed; the protective effect of Rosuvastatin to be dose dependent. In conclusion, the heart failure of aged SHRs that was developed during the end stage of hypertension could be ameliorated by Rosuvastatin.

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