Open AccessRosuvastatin‐attenuated heart failure in aged spontaneously hypertensive rats via PKC α/β2 signal pathway
Author(s) -
Qiu Zhaohui,
Zhang Wenbin,
Fan Fan,
Li Hua,
Wu Chaoneng,
Ye Yong,
Du Qijun,
Li Zheng,
Hu Xiaona,
Zhao Gang,
Sun Aijun,
Bao Zhijun,
Ge Junbo
Publication year - 2012
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/j.1582-4934.2012.01632.x
Subject(s) - phospholamban , medicine , heart failure , serca , endocrinology , chelerythrine , ryanodine receptor , ejection fraction , brain natriuretic peptide , natriuretic peptide , chemistry , protein kinase c , cardiology , calcium , phosphorylation , enzyme , atpase , biochemistry
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 ( SHR s) 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 ( WKY s) as controls. After an 8‐week treatment, the systolic blood pressure ( SBP ) and echocardiographic features were evaluated; m RNA level of B‐type natriuretic peptide ( BNP ) and plasma NT ‐pro BNP concentration were measured; the heart tissues were observed under electron microscope ( EM ); myocardial sarcoplasmic reticulum Ca 2+ 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 ( NCX 1), Ca 2+ /calmodulin‐dependent protein kinase II ( Ca MK II) and protein phosphatase inhibitor‐1 ( PPI ‐1) were detected by Western blot and RT ‐q PCR ; and the total and phosphorylation of protein kinase Cα/β ( PKC α/β) were measured. Aged SHR s 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 ‐pro BNP 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 NCX 1 increased significantly with up‐regulation of PPI ‐1 and down‐regulation of Ca MK II, whereas that of RyR2 decreased. Rosuvastatin was found to ameliorate the heart failure in aged SHR s and to improve changes in SERCA ‐2a, PLB , RyR2, NCX 1, Ca MK II and PPI ‐1; PKC α/β2 signal pathway to be suppressed; the protective effect of Rosuvastatin to be dose dependent. In conclusion, the heart failure of aged SHR s that was developed during the end stage of hypertension could be ameliorated by Rosuvastatin.