Rosuvastatin-attenuated heart failure in aged spontaneously hypertensive ratsviaPKCα/β2 signal pathway

Autor: Junbo Ge, Yong Ye, Zheng Li, Gang Zhao, Xiaona Hu, Chaoneng Wu, Wenbin Zhang, Hua Li, Fan Fan, Aijun Sun, Qijun Du, Zhaohui Qiu, Zhijun Bao
Rok vydání: 2012
Předmět:
Male
Aging
heart failure
Blood Pressure
Rats
Inbred WKY
Ryanodine receptor 2
Ventricular Function
Left
Myofibrils
Rats
Inbred SHR
Natriuretic Peptide
Brain
Phosphorylation
Rosuvastatin Calcium
phospholamban
Sulfonamides
Mitochondria
Up-Regulation
Phospholamban
sarcoplasmic reticulum calcium pump
Sarcoplasmic Reticulum
Hypertension
cardiovascular system
Molecular Medicine
Signal Transduction
medicine.drug
spontaneously hypertensive rat
medicine.medical_specialty
Protein Kinase C-alpha
sodium–calcium exchanger
Down-Regulation
Sodium-Calcium Exchanger
Sarcoplasmic Reticulum Calcium-Transporting ATPases
Rosuvastatin
Electron Transport Complex IV
Spontaneously hypertensive rat
Ca2+/calmodulin-dependent protein kinase
Internal medicine
protein kinase Cα/β2
Protein Kinase C beta
medicine
Animals
RNA
Messenger
cardiovascular diseases
business.industry
Calcium-Binding Proteins
Proteins
Ryanodine Receptor Calcium Release Channel
Stroke Volume
Original Articles
Cell Biology
medicine.disease
Peptide Fragments
Rats
Fluorobenzenes
Pyrimidines
Blood pressure
Endocrinology
Heart failure
ryanodine receptor2
Calcium-Calmodulin-Dependent Protein Kinase Type 2
business
Zdroj: Journal of Cellular and Molecular Medicine
ISSN: 1582-1838
DOI: 10.1111/j.1582-4934.2012.01632.x
Popis: 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 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 (NCX1), Ca(2+)/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.
Databáze: OpenAIRE
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