Rosuvastatin-attenuated heart failure in aged spontaneously hypertensive rats via PKCα/β2 signal pathway
Zhaohui Qiu
Shanghai Institute of Cardiovascular Diseases of Zhongshan Hospital, Fudan University, Shanghai, China
Institute of Biomedical Science, Fudan University, Shanghai, China
Huadong Hospital, Fudan University, Shanghai, China
These authors contributed equally to this work.Search for more papers by this authorWenbin Zhang
Shanghai Institute of Cardiovascular Diseases of Zhongshan Hospital, Fudan University, Shanghai, China
Institute of Biomedical Science, Fudan University, Shanghai, China
These authors contributed equally to this work.Search for more papers by this authorFan Fan
Shanghai Institute of Cardiovascular Diseases of Zhongshan Hospital, Fudan University, Shanghai, China
Institute of Biomedical Science, Fudan University, Shanghai, China
Search for more papers by this authorHua Li
Shanghai Institute of Cardiovascular Diseases of Zhongshan Hospital, Fudan University, Shanghai, China
Institute of Biomedical Science, Fudan University, Shanghai, China
Search for more papers by this authorChaoneng Wu
Shanghai Institute of Cardiovascular Diseases of Zhongshan Hospital, Fudan University, Shanghai, China
Institute of Biomedical Science, Fudan University, Shanghai, China
Search for more papers by this authorYong Ye
Institute of Biomedical Science, Fudan University, Shanghai, China
Search for more papers by this authorQijun Du
Shanghai Institute of Cardiovascular Diseases of Zhongshan Hospital, Fudan University, Shanghai, China
Institute of Biomedical Science, Fudan University, Shanghai, China
Search for more papers by this authorGang Zhao
Shanghai Institute of Cardiovascular Diseases of Zhongshan Hospital, Fudan University, Shanghai, China
Institute of Biomedical Science, Fudan University, Shanghai, China
Search for more papers by this authorAijun Sun
Shanghai Institute of Cardiovascular Diseases of Zhongshan Hospital, Fudan University, Shanghai, China
Institute of Biomedical Science, Fudan University, Shanghai, China
Search for more papers by this authorCorresponding Author
Junbo Ge
Shanghai Institute of Cardiovascular Diseases of Zhongshan Hospital, Fudan University, Shanghai, China
Institute of Biomedical Science, Fudan University, Shanghai, China
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: [email protected]
Search for more papers by this authorZhaohui Qiu
Shanghai Institute of Cardiovascular Diseases of Zhongshan Hospital, Fudan University, Shanghai, China
Institute of Biomedical Science, Fudan University, Shanghai, China
Huadong Hospital, Fudan University, Shanghai, China
These authors contributed equally to this work.Search for more papers by this authorWenbin Zhang
Shanghai Institute of Cardiovascular Diseases of Zhongshan Hospital, Fudan University, Shanghai, China
Institute of Biomedical Science, Fudan University, Shanghai, China
These authors contributed equally to this work.Search for more papers by this authorFan Fan
Shanghai Institute of Cardiovascular Diseases of Zhongshan Hospital, Fudan University, Shanghai, China
Institute of Biomedical Science, Fudan University, Shanghai, China
Search for more papers by this authorHua Li
Shanghai Institute of Cardiovascular Diseases of Zhongshan Hospital, Fudan University, Shanghai, China
Institute of Biomedical Science, Fudan University, Shanghai, China
Search for more papers by this authorChaoneng Wu
Shanghai Institute of Cardiovascular Diseases of Zhongshan Hospital, Fudan University, Shanghai, China
Institute of Biomedical Science, Fudan University, Shanghai, China
Search for more papers by this authorYong Ye
Institute of Biomedical Science, Fudan University, Shanghai, China
Search for more papers by this authorQijun Du
Shanghai Institute of Cardiovascular Diseases of Zhongshan Hospital, Fudan University, Shanghai, China
Institute of Biomedical Science, Fudan University, Shanghai, China
Search for more papers by this authorGang Zhao
Shanghai Institute of Cardiovascular Diseases of Zhongshan Hospital, Fudan University, Shanghai, China
Institute of Biomedical Science, Fudan University, Shanghai, China
Search for more papers by this authorAijun Sun
Shanghai Institute of Cardiovascular Diseases of Zhongshan Hospital, Fudan University, Shanghai, China
Institute of Biomedical Science, Fudan University, Shanghai, China
Search for more papers by this authorCorresponding Author
Junbo Ge
Shanghai Institute of Cardiovascular Diseases of Zhongshan Hospital, Fudan University, Shanghai, China
Institute of Biomedical Science, Fudan University, Shanghai, China
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: [email protected]
Search for more papers by this authorAbstract
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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